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Masatoshi Fujita - One of the best experts on this subject based on the ideXlab platform.

  • Pericardial Fluid and serum biomarkers equally predict ventricular dysfunction
    Asian cardiovascular & thoracic annals, 2013
    Co-Authors: Sofia Amjad, Masatoshi Fujita, Shahid Ahmed Sami, Muhammad Nageeb Basir, Kamran Hameed, Hakeemuddin Razi Ahmad
    Abstract:

    Background: serum level of amino-terminal pro-B-type natriuretic peptide, a cardiac hormone produced by the heart, is elevated in patients with left ventricular dysfunction. The purpose of this study was to compare the abilities of serum and Pericardial Fluid levels of amino-terminal pro-B-type natriuretic peptide to detect the left ventricular systolic dysfunction determined by echocardiography.Methods: 50 patients undergoing coronary artery bypass grafting were included in this study. Left ventricular systolic function was assessed using echocardiography before coronary artery bypass grafting. The samples of serum and Pericardial Fluid were collected during surgery, and amino-terminal pro-B-type natriuretic peptide levels were assessed by an electrochemiluminescence immunoassay. The log value of amino-terminal pro-B-type natriuretic peptide concentrations was calculated.Results: the Pericardial Fluid levels of log amino-terminal pro-B-type natriuretic peptide were significantly elevated compared to the ...

  • Pericardial Fluid level of heart type cytoplasmic fatty acid binding protein h fabp is an indicator of severe myocardial ischemia
    International Journal of Cardiology, 2004
    Co-Authors: Keiichi Tambara, Masatoshi Fujita, Shoichi Miyamoto, Kazunobu Nishimura, Kazuhiko Doi, Masashi Komeda
    Abstract:

    Abstract Background: Heart-type cytoplasmic fatty acid-binding protein (H-FABP) has been reported as a sensitive and specific marker for the early diagnosis of acute myocardial infarction. Our hypothesis was that serum or Pericardial Fluid levels of H-FABP can reflect not only myocardial infarction but also myocardial ischemia. Methods: A total of 34 patients with unstable angina, who had anginal symptoms and/or ST-changes in ECG monitoring within 24 h before operation, were classified into group A ( n =17), and those without these symptoms and changes into group B ( n =17). Blood and Pericardial Fluid samples were obtained immediately after median sternotomy, and serum and Pericardial Fluid levels of creatine kinase-MB, cardiac troponin-T, and H-FABP were measured. Results: Serum H-FABP levels were slightly elevated compared with their normal values in both groups. While they showed no difference between groups A and B (group A vs. B: 8.5±1.0 vs. 7.1±0.7 ng/ml, P =0.25), Pericardial Fluid levels of H-FABP were significantly higher in group A than in group B (16.3±2.0 vs. 9.6±1.0 ng/ml, P =0.0046). H-FABP showed a weak correlation between its serum levels and Pericardial Fluid levels ( r =0.40). Conclusions: Pericardial Fluid levels of H-FABP reflect myocardial ischemia occurring within 24 h of their measurements. H-FABP may be secreted into the interstitial space by increased permeability of the myocardial cell membrane associated with severe myocardial ischemia. Thus, Pericardial Fluid reflects pathophysiological conditions of cardiomyocytes more sensitively than circulating blood.

  • Increased Pericardial Fluid concentrations of the mature form of adrenomedullin in patients with cardiac remodelling
    Heart, 2002
    Co-Authors: Keiichi Tambara, Masatoshi Fujita, Noritoshi Nagaya, Shoichi Miyamoto, Atsushi Iwakura, Genichi Sakaguchi, Kazunobu Nishimura, Kenji Kangawa, Masashi Komeda
    Abstract:

    Background: There is evidence that adrenomedullin has autocrine or paracrine activities that oppose cardiac remodelling. However, it remains unclear whether it exerts those local functions in heart failure patients. Objective: To investigate the relation between plasma and Pericardial Fluid concentrations of adrenomedullin and left ventricular haemodynamic variables. Design: Samples of plasma and Pericardial Fluid were obtained from 50 patients undergoing cardiac surgery. They were classified into two groups: group N (n = 27) with a left ventricular end diastolic volume index (LVEDVI) ≤ 90 ml/m2; and group R (n = 23) with LVEDVI > 90 ml/m2. Plasma and Pericardial Fluid concentrations of total adrenomedullin (tAM) and mature adrenomedullin (mAM) were measured and related to the preoperative haemodynamic variables. Results: Pericardial Fluid concentrations of mAM were much higher than the plasma concentration in both group N and group R (mean (SEM), 10.6 (1.7) v 3.3 (0.2) fmol/ml, p = 0.0001; and 21.2 (2.8) v 3.9 (0.3) fmol/ml, p < 0.0001, respectively). The ratio mAM/tAM in Pericardial Fluid was significantly higher than in plasma (0.56 (0.02) v 0.28 (0.02), p < 0.0001). Pericardial Fluid concentrations of mAM, but not plasma concentrations, were significantly correlated with LVEDVI, left ventricular end systolic volume index, left ventricular ejection fraction, and left ventricular mass index (r = 0.60, 0.63, −0.54, and 0.47, respectively). Conclusions: Raised Pericardial Fluid concentrations of mAM may reflect the actions of adrenomedullin as a local mediator against cardiac remodelling in patients with left ventricular dysfunction.

  • Pericardial Fluid from patients with ischemic heart disease induces myocardial cell apoptotis via an oxidant stress sensitive p38 mitogen activated protein kinase pathway
    Journal of Molecular and Cellular Cardiology, 2001
    Co-Authors: Atsushi Iwakura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Shigetake Sasayama, Shinya Toyokuni, Masashi Komeda
    Abstract:

    Factors produced by the heart are accumulated at high concentrations in Pericardial Fluid. We recently reported that Pericardial Fluid from patients with ischemic heart disease induces apoptosis in an F2 cell line. To characterize factors in Pericardial Fluid from patients with ischemic heart disease, we investigated signaling pathways by which this Pericardial Fluid induces apoptosis in cardiac myocytes. Pericardial Fluid from patients with ischemic heart disease markedly increased the percentage of TUNEL-positive myocytes compared with fetal bovine serum. Apoptosis was also confirmed by ladder formation and morphologic features. Apoptosis mediated by this Pericardial Fluid occurs as readily in cardiac myocytes prepared from neonatal mice nullizygous for p53 as in wild-type littermates. This indicates that p53 is not required for this process. We have found that Pericardial Fluid from ischemic heart disease elicits a robust increase in phosphorylation of p38 mitogen-activated protein kinase. Specific inhibition of the p38 mitogen-activated protein kinase pathway with SB 203580 almost completely blocked apoptosis mediated by Pericardial Fluid from ischemic heart disease. Activation of p38 mitogen-activated protein kinase is caused by cellular stress, including oxidants. We have also found that anti-oxidant catalase inhibited Pericardial Fluid-induced activation of p38 mitogen-activated protein kinase and apoptosis. These findings demonstrate that myocardial cell apoptosis induced by Pericardial Fluid from patients with ischemic heart disease is mediated by an oxidant stress-sensitive p38 mitogen-activated protein kinase pathway. A possible application of SB 203580 to preserve cardiac function in patients with ischemic heart disease should be discussed.

  • Pericardial Fluid from patients with ischemic heart disease accelerates the growth of human vascular smooth muscle cells
    Japanese Circulation Journal-english Edition, 2000
    Co-Authors: Takeshi Yoneda, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Terumitsu Tanaka, Yasuki Kihara, Miyako Inanami, Shigetake Sasayama
    Abstract:

    The strong association between severe coronary stenosis and collateral growth continues to be a paradigm in this field of investigation. The present study was based on the hypothesis that angiogenic growth factors are produced by ischemic cardiac tissue, are diffusible and more concentrated in Pericardial Fluid, and accelerate the growth of vascular smooth muscle cells (VSMC). Pericardial Fluid from 17 patients with stable or unstable angina or acute myocardial infarction (group A) and from 10 patients with nonischemic heart disease (group B) were collected at the time of open heart surgery. Cultured human aortic VSMC were plated at the third passage at a density of 5x10(3)/100 microl and allowed to attach for 24 h. The 3-day growth assay was preceded by 72 h of growth arrest with 0.4% fetal calf serum (FCS). Growth was restarted by the addition of 90 microl of medium containing 0.4% FCS, and 1O microl of each Pericardial Fluid. Cell counts on triplicate wells were performed using a dimethylthiazol (MTT) method on days 0 and 3. The effect of Pericardial Fluid on the growth of VSMC was evaluated as a ratio (R) of cell numbers on day 3 to those on day 0. The concentration of basic fibroblast growth factor (bFGF) in Pericardial Fluid was measured by an enzyme-linked immunosorbent assay. The concentration of bFGF in Pericardial Fluid of group A was 633+/-127 pg/ml, and significantly (p=0.003) higher than that of group B (86+/-23 pg/ml). R in group A was 2.29+/-0.18 and significantly (p=0.019) higher than that in group B (1.68+/-0.11). The level of bFGF positively correlated with R (p=0.009). These findings indicate that Pericardial Fluid from patients with ischemic heart disease contains some substances that mediate collateral development, and bFGF might be one of them.

Shigetake Sasayama - One of the best experts on this subject based on the ideXlab platform.

  • Pericardial Fluid from patients with ischemic heart disease induces myocardial cell apoptotis via an oxidant stress sensitive p38 mitogen activated protein kinase pathway
    Journal of Molecular and Cellular Cardiology, 2001
    Co-Authors: Atsushi Iwakura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Shigetake Sasayama, Shinya Toyokuni, Masashi Komeda
    Abstract:

    Factors produced by the heart are accumulated at high concentrations in Pericardial Fluid. We recently reported that Pericardial Fluid from patients with ischemic heart disease induces apoptosis in an F2 cell line. To characterize factors in Pericardial Fluid from patients with ischemic heart disease, we investigated signaling pathways by which this Pericardial Fluid induces apoptosis in cardiac myocytes. Pericardial Fluid from patients with ischemic heart disease markedly increased the percentage of TUNEL-positive myocytes compared with fetal bovine serum. Apoptosis was also confirmed by ladder formation and morphologic features. Apoptosis mediated by this Pericardial Fluid occurs as readily in cardiac myocytes prepared from neonatal mice nullizygous for p53 as in wild-type littermates. This indicates that p53 is not required for this process. We have found that Pericardial Fluid from ischemic heart disease elicits a robust increase in phosphorylation of p38 mitogen-activated protein kinase. Specific inhibition of the p38 mitogen-activated protein kinase pathway with SB 203580 almost completely blocked apoptosis mediated by Pericardial Fluid from ischemic heart disease. Activation of p38 mitogen-activated protein kinase is caused by cellular stress, including oxidants. We have also found that anti-oxidant catalase inhibited Pericardial Fluid-induced activation of p38 mitogen-activated protein kinase and apoptosis. These findings demonstrate that myocardial cell apoptosis induced by Pericardial Fluid from patients with ischemic heart disease is mediated by an oxidant stress-sensitive p38 mitogen-activated protein kinase pathway. A possible application of SB 203580 to preserve cardiac function in patients with ischemic heart disease should be discussed.

  • Pericardial Fluid from patients with ischemic heart disease accelerates the growth of human vascular smooth muscle cells
    Japanese Circulation Journal-english Edition, 2000
    Co-Authors: Takeshi Yoneda, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Terumitsu Tanaka, Yasuki Kihara, Miyako Inanami, Shigetake Sasayama
    Abstract:

    The strong association between severe coronary stenosis and collateral growth continues to be a paradigm in this field of investigation. The present study was based on the hypothesis that angiogenic growth factors are produced by ischemic cardiac tissue, are diffusible and more concentrated in Pericardial Fluid, and accelerate the growth of vascular smooth muscle cells (VSMC). Pericardial Fluid from 17 patients with stable or unstable angina or acute myocardial infarction (group A) and from 10 patients with nonischemic heart disease (group B) were collected at the time of open heart surgery. Cultured human aortic VSMC were plated at the third passage at a density of 5x10(3)/100 microl and allowed to attach for 24 h. The 3-day growth assay was preceded by 72 h of growth arrest with 0.4% fetal calf serum (FCS). Growth was restarted by the addition of 90 microl of medium containing 0.4% FCS, and 1O microl of each Pericardial Fluid. Cell counts on triplicate wells were performed using a dimethylthiazol (MTT) method on days 0 and 3. The effect of Pericardial Fluid on the growth of VSMC was evaluated as a ratio (R) of cell numbers on day 3 to those on day 0. The concentration of basic fibroblast growth factor (bFGF) in Pericardial Fluid was measured by an enzyme-linked immunosorbent assay. The concentration of bFGF in Pericardial Fluid of group A was 633+/-127 pg/ml, and significantly (p=0.003) higher than that of group B (86+/-23 pg/ml). R in group A was 2.29+/-0.18 and significantly (p=0.019) higher than that in group B (1.68+/-0.11). The level of bFGF positively correlated with R (p=0.009). These findings indicate that Pericardial Fluid from patients with ischemic heart disease contains some substances that mediate collateral development, and bFGF might be one of them.

  • Myocardial ischemia enhances the expression of acidic fibroblast growth factor in human Pericardial Fluid
    Heart and Vessels, 2000
    Co-Authors: Atsushi Iwakura, Keiichi Tambara, Shoichi Miyamoto, M Fujita, Koji Hasegawa, Ryuji Nohara, Shigetake Sasayama, Masaki Ikemoto, Ario Yamazato, Masashi Komeda
    Abstract:

    Acidic fibroblast growth factor (FGF) is a potent mitogen that can induce angiogenesis in vivo. We have recently reported a marked increase of basic FGF in the Pericardial Fluid of patients with severe coronary stenosis and an increase in vascular endothelial growth factor (VEGF) in the Pericardial Fluid of patients with severe myocardial ischemia. The purpose of this study was to evaluate whether acidic FGF levels in the Pericardial Fluid are associated with severe myocardial ischemia. Immediately after incision of the pericardium in 48 patients during open-heart surgery, 3–5 ml of Pericardial Fluid was obtained. Concentrations of basic FGF and VEGF in the Pericardial Fluid were measured using an enzyme-linked immunosorbent assay (ELISA). The ELISA system for human acidic FGF was newly developed using a rabbit antibovine acidic FGF antibody. The patients were divided into three groups (group A: 13 patients undergoing emergency coronary artery bypass grafting (CABG) for unstable angina; group B: 17 patients undergoing elective CABG for stable angina; group C: 18 patients undergoing nonischemic open-heart surgery). The VEGF level in the Pericardial Fluid in group A was 68 ± 59 pg/ml, which was significantly higher than 33 ± 9 pg/ml in group B and 31 ± 20 pg/ml in group C ( P < 0.05). The concentrations of basic FGF in the Pericardial Fluid in groups A and B were 722 ± 601 and 773 ± 763 pg/ml, respectively, significantly higher than 263 ± 349 pg/ml in group C. The Pericardial acidic FGF level in group A was 4 291 ± 2 336 pg/ml, which was also significantly higher than 2 386 ± 1 048 pg/ml in group B and 2 589 ± 990 pg/ml in group C ( P < 0.05). The acidic FGF level correlated well with the level of VEGF ( r = 0.61, P < 0.0001). It is concluded that the level of acidic FGF in Pericardial Fluid is associated with severe myocardial ischemia. This result indicates that the release of acidic FGF from the myocardial tissue into Pericardial Fluid is closely related to severe myocardial ischemia.

  • Pericardial Fluid from patients with unstable angina induces vascular endothelial cell apoptosis.
    Journal of the American College of Cardiology, 2000
    Co-Authors: Atsushi Iwakura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Shigetake Sasayama, Masashi Komeda
    Abstract:

    Abstract OBJECTIVES The purpose of this study was to investigate whether Pericardial Fluid from patients with unstable angina (UA) would modulate vascular endothelial cell survival. BACKGROUND Apoptosis of vascular endothelial cells promotes the coagulation process, playing an important role in the formation of coronary arterial thrombi. However, little is known about the mechanisms of vascular endothelial cell death in acute coronary syndrome. We hypothesized that factors inducing apoptosis are produced by the ischemic heart and accumulated in high concentrations in Pericardial Fluid. METHODS Pericardial Fluid was obtained during coronary artery bypass surgery from patients with UA (group A, n = 8) and those with stable angina (group B, n = 23). A survival assay of F2 cells from a mouse vascular endothelial cell line was performed in the presence of 10% Pericardial Fluid from each patient. RESULTS Pericardial Fluid levels of vascular endothelial growth factor were significantly higher in group A than in group B, indicating that group A had more ischemic insults than group B. Pericardial Fluid from group A, but not from group B, markedly induced F2 cell death (cell survival relative to fetal bovine serum; group A: 33 ± 26% vs. group B: 91 ± 22%, p CONCLUSIONS Factors that induce vascular endothelial cell apoptosis are secreted into the Pericardial space from the hearts of patients with UA. These factors are large complexes or unknown new proteins larger than 100 kDa.

  • Marked Elevation of Brain Natriuretic Peptide Levels in Pericardial Fluid Is Closely Associated With Left Ventricular Dysfunction
    Journal of the American College of Cardiology, 1998
    Co-Authors: Terumitsu Tanaka, Masatoshi Fujita, Koji Hasegawa, Ryuji Nohara, Ario Yamazato, Shunichi Tamaki, Yasuki Kihara, Shigetake Sasayama
    Abstract:

    Abstract Objectives. The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in Pericardial Fluid. Background. ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides. Methods. With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and Pericardial Fluid simultaneously in 28 patients during coronary artery bypass graft surgery. Results. The Pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or Pericardial Fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or Pericardial Fluid. Both plasma and Pericardial Fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP Pericardial Fluid levels had closer relations with LVEDVI (r = 0.679, p Conclusions. BNP levels in Pericardial Fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the Pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.

Masashi Komeda - One of the best experts on this subject based on the ideXlab platform.

  • Pericardial Fluid level of heart type cytoplasmic fatty acid binding protein h fabp is an indicator of severe myocardial ischemia
    International Journal of Cardiology, 2004
    Co-Authors: Keiichi Tambara, Masatoshi Fujita, Shoichi Miyamoto, Kazunobu Nishimura, Kazuhiko Doi, Masashi Komeda
    Abstract:

    Abstract Background: Heart-type cytoplasmic fatty acid-binding protein (H-FABP) has been reported as a sensitive and specific marker for the early diagnosis of acute myocardial infarction. Our hypothesis was that serum or Pericardial Fluid levels of H-FABP can reflect not only myocardial infarction but also myocardial ischemia. Methods: A total of 34 patients with unstable angina, who had anginal symptoms and/or ST-changes in ECG monitoring within 24 h before operation, were classified into group A ( n =17), and those without these symptoms and changes into group B ( n =17). Blood and Pericardial Fluid samples were obtained immediately after median sternotomy, and serum and Pericardial Fluid levels of creatine kinase-MB, cardiac troponin-T, and H-FABP were measured. Results: Serum H-FABP levels were slightly elevated compared with their normal values in both groups. While they showed no difference between groups A and B (group A vs. B: 8.5±1.0 vs. 7.1±0.7 ng/ml, P =0.25), Pericardial Fluid levels of H-FABP were significantly higher in group A than in group B (16.3±2.0 vs. 9.6±1.0 ng/ml, P =0.0046). H-FABP showed a weak correlation between its serum levels and Pericardial Fluid levels ( r =0.40). Conclusions: Pericardial Fluid levels of H-FABP reflect myocardial ischemia occurring within 24 h of their measurements. H-FABP may be secreted into the interstitial space by increased permeability of the myocardial cell membrane associated with severe myocardial ischemia. Thus, Pericardial Fluid reflects pathophysiological conditions of cardiomyocytes more sensitively than circulating blood.

  • Increased Pericardial Fluid concentrations of the mature form of adrenomedullin in patients with cardiac remodelling
    Heart, 2002
    Co-Authors: Keiichi Tambara, Masatoshi Fujita, Noritoshi Nagaya, Shoichi Miyamoto, Atsushi Iwakura, Genichi Sakaguchi, Kazunobu Nishimura, Kenji Kangawa, Masashi Komeda
    Abstract:

    Background: There is evidence that adrenomedullin has autocrine or paracrine activities that oppose cardiac remodelling. However, it remains unclear whether it exerts those local functions in heart failure patients. Objective: To investigate the relation between plasma and Pericardial Fluid concentrations of adrenomedullin and left ventricular haemodynamic variables. Design: Samples of plasma and Pericardial Fluid were obtained from 50 patients undergoing cardiac surgery. They were classified into two groups: group N (n = 27) with a left ventricular end diastolic volume index (LVEDVI) ≤ 90 ml/m2; and group R (n = 23) with LVEDVI > 90 ml/m2. Plasma and Pericardial Fluid concentrations of total adrenomedullin (tAM) and mature adrenomedullin (mAM) were measured and related to the preoperative haemodynamic variables. Results: Pericardial Fluid concentrations of mAM were much higher than the plasma concentration in both group N and group R (mean (SEM), 10.6 (1.7) v 3.3 (0.2) fmol/ml, p = 0.0001; and 21.2 (2.8) v 3.9 (0.3) fmol/ml, p < 0.0001, respectively). The ratio mAM/tAM in Pericardial Fluid was significantly higher than in plasma (0.56 (0.02) v 0.28 (0.02), p < 0.0001). Pericardial Fluid concentrations of mAM, but not plasma concentrations, were significantly correlated with LVEDVI, left ventricular end systolic volume index, left ventricular ejection fraction, and left ventricular mass index (r = 0.60, 0.63, −0.54, and 0.47, respectively). Conclusions: Raised Pericardial Fluid concentrations of mAM may reflect the actions of adrenomedullin as a local mediator against cardiac remodelling in patients with left ventricular dysfunction.

  • Pericardial Fluid from patients with ischemic heart disease induces myocardial cell apoptotis via an oxidant stress sensitive p38 mitogen activated protein kinase pathway
    Journal of Molecular and Cellular Cardiology, 2001
    Co-Authors: Atsushi Iwakura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Shigetake Sasayama, Shinya Toyokuni, Masashi Komeda
    Abstract:

    Factors produced by the heart are accumulated at high concentrations in Pericardial Fluid. We recently reported that Pericardial Fluid from patients with ischemic heart disease induces apoptosis in an F2 cell line. To characterize factors in Pericardial Fluid from patients with ischemic heart disease, we investigated signaling pathways by which this Pericardial Fluid induces apoptosis in cardiac myocytes. Pericardial Fluid from patients with ischemic heart disease markedly increased the percentage of TUNEL-positive myocytes compared with fetal bovine serum. Apoptosis was also confirmed by ladder formation and morphologic features. Apoptosis mediated by this Pericardial Fluid occurs as readily in cardiac myocytes prepared from neonatal mice nullizygous for p53 as in wild-type littermates. This indicates that p53 is not required for this process. We have found that Pericardial Fluid from ischemic heart disease elicits a robust increase in phosphorylation of p38 mitogen-activated protein kinase. Specific inhibition of the p38 mitogen-activated protein kinase pathway with SB 203580 almost completely blocked apoptosis mediated by Pericardial Fluid from ischemic heart disease. Activation of p38 mitogen-activated protein kinase is caused by cellular stress, including oxidants. We have also found that anti-oxidant catalase inhibited Pericardial Fluid-induced activation of p38 mitogen-activated protein kinase and apoptosis. These findings demonstrate that myocardial cell apoptosis induced by Pericardial Fluid from patients with ischemic heart disease is mediated by an oxidant stress-sensitive p38 mitogen-activated protein kinase pathway. A possible application of SB 203580 to preserve cardiac function in patients with ischemic heart disease should be discussed.

  • Myocardial ischemia enhances the expression of acidic fibroblast growth factor in human Pericardial Fluid
    Heart and Vessels, 2000
    Co-Authors: Atsushi Iwakura, Keiichi Tambara, Shoichi Miyamoto, M Fujita, Koji Hasegawa, Ryuji Nohara, Shigetake Sasayama, Masaki Ikemoto, Ario Yamazato, Masashi Komeda
    Abstract:

    Acidic fibroblast growth factor (FGF) is a potent mitogen that can induce angiogenesis in vivo. We have recently reported a marked increase of basic FGF in the Pericardial Fluid of patients with severe coronary stenosis and an increase in vascular endothelial growth factor (VEGF) in the Pericardial Fluid of patients with severe myocardial ischemia. The purpose of this study was to evaluate whether acidic FGF levels in the Pericardial Fluid are associated with severe myocardial ischemia. Immediately after incision of the pericardium in 48 patients during open-heart surgery, 3–5 ml of Pericardial Fluid was obtained. Concentrations of basic FGF and VEGF in the Pericardial Fluid were measured using an enzyme-linked immunosorbent assay (ELISA). The ELISA system for human acidic FGF was newly developed using a rabbit antibovine acidic FGF antibody. The patients were divided into three groups (group A: 13 patients undergoing emergency coronary artery bypass grafting (CABG) for unstable angina; group B: 17 patients undergoing elective CABG for stable angina; group C: 18 patients undergoing nonischemic open-heart surgery). The VEGF level in the Pericardial Fluid in group A was 68 ± 59 pg/ml, which was significantly higher than 33 ± 9 pg/ml in group B and 31 ± 20 pg/ml in group C ( P < 0.05). The concentrations of basic FGF in the Pericardial Fluid in groups A and B were 722 ± 601 and 773 ± 763 pg/ml, respectively, significantly higher than 263 ± 349 pg/ml in group C. The Pericardial acidic FGF level in group A was 4 291 ± 2 336 pg/ml, which was also significantly higher than 2 386 ± 1 048 pg/ml in group B and 2 589 ± 990 pg/ml in group C ( P < 0.05). The acidic FGF level correlated well with the level of VEGF ( r = 0.61, P < 0.0001). It is concluded that the level of acidic FGF in Pericardial Fluid is associated with severe myocardial ischemia. This result indicates that the release of acidic FGF from the myocardial tissue into Pericardial Fluid is closely related to severe myocardial ischemia.

  • Pericardial Fluid from patients with unstable angina induces vascular endothelial cell apoptosis.
    Journal of the American College of Cardiology, 2000
    Co-Authors: Atsushi Iwakura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Shigetake Sasayama, Masashi Komeda
    Abstract:

    Abstract OBJECTIVES The purpose of this study was to investigate whether Pericardial Fluid from patients with unstable angina (UA) would modulate vascular endothelial cell survival. BACKGROUND Apoptosis of vascular endothelial cells promotes the coagulation process, playing an important role in the formation of coronary arterial thrombi. However, little is known about the mechanisms of vascular endothelial cell death in acute coronary syndrome. We hypothesized that factors inducing apoptosis are produced by the ischemic heart and accumulated in high concentrations in Pericardial Fluid. METHODS Pericardial Fluid was obtained during coronary artery bypass surgery from patients with UA (group A, n = 8) and those with stable angina (group B, n = 23). A survival assay of F2 cells from a mouse vascular endothelial cell line was performed in the presence of 10% Pericardial Fluid from each patient. RESULTS Pericardial Fluid levels of vascular endothelial growth factor were significantly higher in group A than in group B, indicating that group A had more ischemic insults than group B. Pericardial Fluid from group A, but not from group B, markedly induced F2 cell death (cell survival relative to fetal bovine serum; group A: 33 ± 26% vs. group B: 91 ± 22%, p CONCLUSIONS Factors that induce vascular endothelial cell apoptosis are secreted into the Pericardial space from the hearts of patients with UA. These factors are large complexes or unknown new proteins larger than 100 kDa.

Ryuji Nohara - One of the best experts on this subject based on the ideXlab platform.

  • Pericardial Fluid from patients with ischemic heart disease induces myocardial cell apoptotis via an oxidant stress sensitive p38 mitogen activated protein kinase pathway
    Journal of Molecular and Cellular Cardiology, 2001
    Co-Authors: Atsushi Iwakura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Shigetake Sasayama, Shinya Toyokuni, Masashi Komeda
    Abstract:

    Factors produced by the heart are accumulated at high concentrations in Pericardial Fluid. We recently reported that Pericardial Fluid from patients with ischemic heart disease induces apoptosis in an F2 cell line. To characterize factors in Pericardial Fluid from patients with ischemic heart disease, we investigated signaling pathways by which this Pericardial Fluid induces apoptosis in cardiac myocytes. Pericardial Fluid from patients with ischemic heart disease markedly increased the percentage of TUNEL-positive myocytes compared with fetal bovine serum. Apoptosis was also confirmed by ladder formation and morphologic features. Apoptosis mediated by this Pericardial Fluid occurs as readily in cardiac myocytes prepared from neonatal mice nullizygous for p53 as in wild-type littermates. This indicates that p53 is not required for this process. We have found that Pericardial Fluid from ischemic heart disease elicits a robust increase in phosphorylation of p38 mitogen-activated protein kinase. Specific inhibition of the p38 mitogen-activated protein kinase pathway with SB 203580 almost completely blocked apoptosis mediated by Pericardial Fluid from ischemic heart disease. Activation of p38 mitogen-activated protein kinase is caused by cellular stress, including oxidants. We have also found that anti-oxidant catalase inhibited Pericardial Fluid-induced activation of p38 mitogen-activated protein kinase and apoptosis. These findings demonstrate that myocardial cell apoptosis induced by Pericardial Fluid from patients with ischemic heart disease is mediated by an oxidant stress-sensitive p38 mitogen-activated protein kinase pathway. A possible application of SB 203580 to preserve cardiac function in patients with ischemic heart disease should be discussed.

  • Pericardial Fluid from patients with ischemic heart disease accelerates the growth of human vascular smooth muscle cells
    Japanese Circulation Journal-english Edition, 2000
    Co-Authors: Takeshi Yoneda, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Terumitsu Tanaka, Yasuki Kihara, Miyako Inanami, Shigetake Sasayama
    Abstract:

    The strong association between severe coronary stenosis and collateral growth continues to be a paradigm in this field of investigation. The present study was based on the hypothesis that angiogenic growth factors are produced by ischemic cardiac tissue, are diffusible and more concentrated in Pericardial Fluid, and accelerate the growth of vascular smooth muscle cells (VSMC). Pericardial Fluid from 17 patients with stable or unstable angina or acute myocardial infarction (group A) and from 10 patients with nonischemic heart disease (group B) were collected at the time of open heart surgery. Cultured human aortic VSMC were plated at the third passage at a density of 5x10(3)/100 microl and allowed to attach for 24 h. The 3-day growth assay was preceded by 72 h of growth arrest with 0.4% fetal calf serum (FCS). Growth was restarted by the addition of 90 microl of medium containing 0.4% FCS, and 1O microl of each Pericardial Fluid. Cell counts on triplicate wells were performed using a dimethylthiazol (MTT) method on days 0 and 3. The effect of Pericardial Fluid on the growth of VSMC was evaluated as a ratio (R) of cell numbers on day 3 to those on day 0. The concentration of basic fibroblast growth factor (bFGF) in Pericardial Fluid was measured by an enzyme-linked immunosorbent assay. The concentration of bFGF in Pericardial Fluid of group A was 633+/-127 pg/ml, and significantly (p=0.003) higher than that of group B (86+/-23 pg/ml). R in group A was 2.29+/-0.18 and significantly (p=0.019) higher than that in group B (1.68+/-0.11). The level of bFGF positively correlated with R (p=0.009). These findings indicate that Pericardial Fluid from patients with ischemic heart disease contains some substances that mediate collateral development, and bFGF might be one of them.

  • Myocardial ischemia enhances the expression of acidic fibroblast growth factor in human Pericardial Fluid
    Heart and Vessels, 2000
    Co-Authors: Atsushi Iwakura, Keiichi Tambara, Shoichi Miyamoto, M Fujita, Koji Hasegawa, Ryuji Nohara, Shigetake Sasayama, Masaki Ikemoto, Ario Yamazato, Masashi Komeda
    Abstract:

    Acidic fibroblast growth factor (FGF) is a potent mitogen that can induce angiogenesis in vivo. We have recently reported a marked increase of basic FGF in the Pericardial Fluid of patients with severe coronary stenosis and an increase in vascular endothelial growth factor (VEGF) in the Pericardial Fluid of patients with severe myocardial ischemia. The purpose of this study was to evaluate whether acidic FGF levels in the Pericardial Fluid are associated with severe myocardial ischemia. Immediately after incision of the pericardium in 48 patients during open-heart surgery, 3–5 ml of Pericardial Fluid was obtained. Concentrations of basic FGF and VEGF in the Pericardial Fluid were measured using an enzyme-linked immunosorbent assay (ELISA). The ELISA system for human acidic FGF was newly developed using a rabbit antibovine acidic FGF antibody. The patients were divided into three groups (group A: 13 patients undergoing emergency coronary artery bypass grafting (CABG) for unstable angina; group B: 17 patients undergoing elective CABG for stable angina; group C: 18 patients undergoing nonischemic open-heart surgery). The VEGF level in the Pericardial Fluid in group A was 68 ± 59 pg/ml, which was significantly higher than 33 ± 9 pg/ml in group B and 31 ± 20 pg/ml in group C ( P < 0.05). The concentrations of basic FGF in the Pericardial Fluid in groups A and B were 722 ± 601 and 773 ± 763 pg/ml, respectively, significantly higher than 263 ± 349 pg/ml in group C. The Pericardial acidic FGF level in group A was 4 291 ± 2 336 pg/ml, which was also significantly higher than 2 386 ± 1 048 pg/ml in group B and 2 589 ± 990 pg/ml in group C ( P < 0.05). The acidic FGF level correlated well with the level of VEGF ( r = 0.61, P < 0.0001). It is concluded that the level of acidic FGF in Pericardial Fluid is associated with severe myocardial ischemia. This result indicates that the release of acidic FGF from the myocardial tissue into Pericardial Fluid is closely related to severe myocardial ischemia.

  • Pericardial Fluid from patients with unstable angina induces vascular endothelial cell apoptosis.
    Journal of the American College of Cardiology, 2000
    Co-Authors: Atsushi Iwakura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Shigetake Sasayama, Masashi Komeda
    Abstract:

    Abstract OBJECTIVES The purpose of this study was to investigate whether Pericardial Fluid from patients with unstable angina (UA) would modulate vascular endothelial cell survival. BACKGROUND Apoptosis of vascular endothelial cells promotes the coagulation process, playing an important role in the formation of coronary arterial thrombi. However, little is known about the mechanisms of vascular endothelial cell death in acute coronary syndrome. We hypothesized that factors inducing apoptosis are produced by the ischemic heart and accumulated in high concentrations in Pericardial Fluid. METHODS Pericardial Fluid was obtained during coronary artery bypass surgery from patients with UA (group A, n = 8) and those with stable angina (group B, n = 23). A survival assay of F2 cells from a mouse vascular endothelial cell line was performed in the presence of 10% Pericardial Fluid from each patient. RESULTS Pericardial Fluid levels of vascular endothelial growth factor were significantly higher in group A than in group B, indicating that group A had more ischemic insults than group B. Pericardial Fluid from group A, but not from group B, markedly induced F2 cell death (cell survival relative to fetal bovine serum; group A: 33 ± 26% vs. group B: 91 ± 22%, p CONCLUSIONS Factors that induce vascular endothelial cell apoptosis are secreted into the Pericardial space from the hearts of patients with UA. These factors are large complexes or unknown new proteins larger than 100 kDa.

  • Marked Elevation of Brain Natriuretic Peptide Levels in Pericardial Fluid Is Closely Associated With Left Ventricular Dysfunction
    Journal of the American College of Cardiology, 1998
    Co-Authors: Terumitsu Tanaka, Masatoshi Fujita, Koji Hasegawa, Ryuji Nohara, Ario Yamazato, Shunichi Tamaki, Yasuki Kihara, Shigetake Sasayama
    Abstract:

    Abstract Objectives. The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in Pericardial Fluid. Background. ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides. Methods. With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and Pericardial Fluid simultaneously in 28 patients during coronary artery bypass graft surgery. Results. The Pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or Pericardial Fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or Pericardial Fluid. Both plasma and Pericardial Fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP Pericardial Fluid levels had closer relations with LVEDVI (r = 0.679, p Conclusions. BNP levels in Pericardial Fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the Pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.

Koji Hasegawa - One of the best experts on this subject based on the ideXlab platform.

  • Pericardial Fluid from patients with ischemic heart disease induces myocardial cell apoptotis via an oxidant stress sensitive p38 mitogen activated protein kinase pathway
    Journal of Molecular and Cellular Cardiology, 2001
    Co-Authors: Atsushi Iwakura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Shigetake Sasayama, Shinya Toyokuni, Masashi Komeda
    Abstract:

    Factors produced by the heart are accumulated at high concentrations in Pericardial Fluid. We recently reported that Pericardial Fluid from patients with ischemic heart disease induces apoptosis in an F2 cell line. To characterize factors in Pericardial Fluid from patients with ischemic heart disease, we investigated signaling pathways by which this Pericardial Fluid induces apoptosis in cardiac myocytes. Pericardial Fluid from patients with ischemic heart disease markedly increased the percentage of TUNEL-positive myocytes compared with fetal bovine serum. Apoptosis was also confirmed by ladder formation and morphologic features. Apoptosis mediated by this Pericardial Fluid occurs as readily in cardiac myocytes prepared from neonatal mice nullizygous for p53 as in wild-type littermates. This indicates that p53 is not required for this process. We have found that Pericardial Fluid from ischemic heart disease elicits a robust increase in phosphorylation of p38 mitogen-activated protein kinase. Specific inhibition of the p38 mitogen-activated protein kinase pathway with SB 203580 almost completely blocked apoptosis mediated by Pericardial Fluid from ischemic heart disease. Activation of p38 mitogen-activated protein kinase is caused by cellular stress, including oxidants. We have also found that anti-oxidant catalase inhibited Pericardial Fluid-induced activation of p38 mitogen-activated protein kinase and apoptosis. These findings demonstrate that myocardial cell apoptosis induced by Pericardial Fluid from patients with ischemic heart disease is mediated by an oxidant stress-sensitive p38 mitogen-activated protein kinase pathway. A possible application of SB 203580 to preserve cardiac function in patients with ischemic heart disease should be discussed.

  • Pericardial Fluid from patients with ischemic heart disease accelerates the growth of human vascular smooth muscle cells
    Japanese Circulation Journal-english Edition, 2000
    Co-Authors: Takeshi Yoneda, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Terumitsu Tanaka, Yasuki Kihara, Miyako Inanami, Shigetake Sasayama
    Abstract:

    The strong association between severe coronary stenosis and collateral growth continues to be a paradigm in this field of investigation. The present study was based on the hypothesis that angiogenic growth factors are produced by ischemic cardiac tissue, are diffusible and more concentrated in Pericardial Fluid, and accelerate the growth of vascular smooth muscle cells (VSMC). Pericardial Fluid from 17 patients with stable or unstable angina or acute myocardial infarction (group A) and from 10 patients with nonischemic heart disease (group B) were collected at the time of open heart surgery. Cultured human aortic VSMC were plated at the third passage at a density of 5x10(3)/100 microl and allowed to attach for 24 h. The 3-day growth assay was preceded by 72 h of growth arrest with 0.4% fetal calf serum (FCS). Growth was restarted by the addition of 90 microl of medium containing 0.4% FCS, and 1O microl of each Pericardial Fluid. Cell counts on triplicate wells were performed using a dimethylthiazol (MTT) method on days 0 and 3. The effect of Pericardial Fluid on the growth of VSMC was evaluated as a ratio (R) of cell numbers on day 3 to those on day 0. The concentration of basic fibroblast growth factor (bFGF) in Pericardial Fluid was measured by an enzyme-linked immunosorbent assay. The concentration of bFGF in Pericardial Fluid of group A was 633+/-127 pg/ml, and significantly (p=0.003) higher than that of group B (86+/-23 pg/ml). R in group A was 2.29+/-0.18 and significantly (p=0.019) higher than that in group B (1.68+/-0.11). The level of bFGF positively correlated with R (p=0.009). These findings indicate that Pericardial Fluid from patients with ischemic heart disease contains some substances that mediate collateral development, and bFGF might be one of them.

  • Myocardial ischemia enhances the expression of acidic fibroblast growth factor in human Pericardial Fluid
    Heart and Vessels, 2000
    Co-Authors: Atsushi Iwakura, Keiichi Tambara, Shoichi Miyamoto, M Fujita, Koji Hasegawa, Ryuji Nohara, Shigetake Sasayama, Masaki Ikemoto, Ario Yamazato, Masashi Komeda
    Abstract:

    Acidic fibroblast growth factor (FGF) is a potent mitogen that can induce angiogenesis in vivo. We have recently reported a marked increase of basic FGF in the Pericardial Fluid of patients with severe coronary stenosis and an increase in vascular endothelial growth factor (VEGF) in the Pericardial Fluid of patients with severe myocardial ischemia. The purpose of this study was to evaluate whether acidic FGF levels in the Pericardial Fluid are associated with severe myocardial ischemia. Immediately after incision of the pericardium in 48 patients during open-heart surgery, 3–5 ml of Pericardial Fluid was obtained. Concentrations of basic FGF and VEGF in the Pericardial Fluid were measured using an enzyme-linked immunosorbent assay (ELISA). The ELISA system for human acidic FGF was newly developed using a rabbit antibovine acidic FGF antibody. The patients were divided into three groups (group A: 13 patients undergoing emergency coronary artery bypass grafting (CABG) for unstable angina; group B: 17 patients undergoing elective CABG for stable angina; group C: 18 patients undergoing nonischemic open-heart surgery). The VEGF level in the Pericardial Fluid in group A was 68 ± 59 pg/ml, which was significantly higher than 33 ± 9 pg/ml in group B and 31 ± 20 pg/ml in group C ( P < 0.05). The concentrations of basic FGF in the Pericardial Fluid in groups A and B were 722 ± 601 and 773 ± 763 pg/ml, respectively, significantly higher than 263 ± 349 pg/ml in group C. The Pericardial acidic FGF level in group A was 4 291 ± 2 336 pg/ml, which was also significantly higher than 2 386 ± 1 048 pg/ml in group B and 2 589 ± 990 pg/ml in group C ( P < 0.05). The acidic FGF level correlated well with the level of VEGF ( r = 0.61, P < 0.0001). It is concluded that the level of acidic FGF in Pericardial Fluid is associated with severe myocardial ischemia. This result indicates that the release of acidic FGF from the myocardial tissue into Pericardial Fluid is closely related to severe myocardial ischemia.

  • Pericardial Fluid from patients with unstable angina induces vascular endothelial cell apoptosis.
    Journal of the American College of Cardiology, 2000
    Co-Authors: Atsushi Iwakura, Masatoshi Fujita, Koji Hasegawa, Tatsuya Sawamura, Ryuji Nohara, Shigetake Sasayama, Masashi Komeda
    Abstract:

    Abstract OBJECTIVES The purpose of this study was to investigate whether Pericardial Fluid from patients with unstable angina (UA) would modulate vascular endothelial cell survival. BACKGROUND Apoptosis of vascular endothelial cells promotes the coagulation process, playing an important role in the formation of coronary arterial thrombi. However, little is known about the mechanisms of vascular endothelial cell death in acute coronary syndrome. We hypothesized that factors inducing apoptosis are produced by the ischemic heart and accumulated in high concentrations in Pericardial Fluid. METHODS Pericardial Fluid was obtained during coronary artery bypass surgery from patients with UA (group A, n = 8) and those with stable angina (group B, n = 23). A survival assay of F2 cells from a mouse vascular endothelial cell line was performed in the presence of 10% Pericardial Fluid from each patient. RESULTS Pericardial Fluid levels of vascular endothelial growth factor were significantly higher in group A than in group B, indicating that group A had more ischemic insults than group B. Pericardial Fluid from group A, but not from group B, markedly induced F2 cell death (cell survival relative to fetal bovine serum; group A: 33 ± 26% vs. group B: 91 ± 22%, p CONCLUSIONS Factors that induce vascular endothelial cell apoptosis are secreted into the Pericardial space from the hearts of patients with UA. These factors are large complexes or unknown new proteins larger than 100 kDa.

  • Marked Elevation of Brain Natriuretic Peptide Levels in Pericardial Fluid Is Closely Associated With Left Ventricular Dysfunction
    Journal of the American College of Cardiology, 1998
    Co-Authors: Terumitsu Tanaka, Masatoshi Fujita, Koji Hasegawa, Ryuji Nohara, Ario Yamazato, Shunichi Tamaki, Yasuki Kihara, Shigetake Sasayama
    Abstract:

    Abstract Objectives. The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in Pericardial Fluid. Background. ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides. Methods. With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and Pericardial Fluid simultaneously in 28 patients during coronary artery bypass graft surgery. Results. The Pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or Pericardial Fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or Pericardial Fluid. Both plasma and Pericardial Fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP Pericardial Fluid levels had closer relations with LVEDVI (r = 0.679, p Conclusions. BNP levels in Pericardial Fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the Pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.