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Piero Anversa - One of the best experts on this subject based on the ideXlab platform.

  • insulin like growth factor 1 attenuates the detrimental impact of nonocclusive Coronary Artery Constriction on the heart
    Circulation Research, 1999
    Co-Authors: Manabu Setoguchi, Jan Kajstura, Annarosa Leri, Xiaowei Wang, Anna Maria Andreoli, Ashwani Malhotra, Piero Anversa
    Abstract:

    Coronary Artery narrowing (CAN) induces tissue injury, which may involve myocyte necrosis and apoptosis. Insulin-like growth factor (IGF)-1 may counteract cell death, modifying the detrimental effects of myocardial ischemia. On this basis, CAN was produced in female FVB.Igf+/- mice and nontransgenic littermates, and the animals were euthanized 7 days later. CAN consisted of an 82% reduction in the vessel luminal cross-sectional area in both groups of mice. Severe left ventricular dysfunction was present in CAN nontransgenic and transgenic mice, but heart and left ventricular weights increased more in littermates than in FVB.Igf+/- mice. Similarly, the changes in chamber volume and diastolic wall stress were greater in nontransgenic mice. Subacute tissue injury, represented by foci of replacement fibrosis, was 2.6-fold higher in CAN littermates than in FVB.Igf+/- mice. Ongoing myocyte necrosis was 5-fold greater in nontransgenic mice, whereas apoptosis was low and did not differ in the 2 groups of mice. In CAN nontransgenic mice, myocyte necrosis was 12-fold more frequent than apoptosis but, in CAN transgenic mice, these 2 types of cell death were comparable. alpha-Myosin and beta-myosin isoform mRNAs were affected by CAN, but alpha-myosin mRNA was reduced more in nontransgenic mice. In conclusion, myocyte necrosis and replacement fibrosis are the prevailing forms of myocardial damage induced by CAN. Constitutive overexpression of IGF-1 attenuates myocyte necrosis and tissue injury, having no effect on cell apoptosis. These factors limit ventricular dilation, myocardial loading, cardiac hypertrophy, and alterations in alpha- and beta-myosin isoform expression.

  • Coronary Artery Constriction in rats: necrotic and apoptotic myocyte death.
    The American Journal of Cardiology, 1998
    Co-Authors: Jan Kajstura, Giorgio Olivetti, Yu Liu, Alessandra Baldini, Annarosa Leri, Piero Anversa
    Abstract:

    The purpose of this study was to determine whether Coronary Artery narrowing was associated with the activation of necrotic and apoptotic myocyte cell death in the myocardium and whether these 2 forms of cell death were restricted to the left ventricle, or involved the other portions of the heart. Coronary Artery narrowing was surgically induced in rats, and the animals were killed from 45 minutes to 12 days after surgery. Myocyte apoptosis was detected by the terminal deoxynucleotidyl transferase assay, confocal microscopy, and deoxyribonucleic acid (DNA) agarose gel electrophoresis. Myocyte necrosis was identified by myosin monoclonal antibody labeling of the cytoplasm. A separate group of animals was treated with trimetazidine in an attempt to interfere with tissue injury. Coronary Artery narrowing was characterized by myocyte apoptosis in the left ventricle and interventricular septum, which progressively increased from 45 minutes to 6 days. However, apoptosis was not observed at 12 days. Conversely, myocyte necrosis reached its maximum value at 1 day and was still present at 12 days. This form of cell death affected not only the left ventricular free wall and interventricular septum, but also the right ventricle. Cell necrosis markedly exceeded apoptosis at all intervals. At the peak of cell death, myocyte necrosis was 52-fold and 33-fold higher than apoptosis in the left ventricle and septum. In conclusion, necrotic myocyte cell death is the prevailing form of damage produced by Coronary Artery narrowing, but apoptotic cell death contributes to the loss of myocytes in the ischemic heart. Trimetazidine treatment attenuated the extent of myocardial damage produced by global ischemia.

  • Ventricular Remodeling Following Coronary Artery Constriction and Hypertension
    Developments in Cardiovascular Medicine, 1996
    Co-Authors: Piero Anversa, Krzysztof Reiss, Jan Kajstura, Giorgio Olivetti, Xun Zhang, Federico Quaini, Edmund H. Sonnenblick
    Abstract:

    In Coronary Artery disease in humans, the severity of the atherosclerotic involvement of the Coronary circulation frequently does not correlate with the impairment in cardiac pump performance, and therefore anatomic condition is a poor predictor of clinical outcome and mortality of the patient population [1–4]. Based on acute studies in animal models [5], the conclusion has been reached that severe reductions in Coronary Artery diameter of nearly 80% are required to create an imbalance between oxygen demand and supply, possibly leading to scattered myocardial damage and the initiation of ischemic cardiomyopathy. However, it has recently been shown that Coronary Artery Constriction of moderate degree may induce diffuse myocytolytic necrosis and marked alterations in ventricular hemodynamics [6]. Moreover, the phenomenon of myocyte cell death was documented to persist with time, chronically affecting the functional and anatomical characteristics of the heart [7,8]. Thus, modest decreases in Coronary diameter may have clinical implications that have not been previously appreciated, and untreated Coronary Artery narrowing may progressively affect the structural integrity of the myocardium.

  • Alterations in angiotensin II receptor mediated signal transduction shortly after Coronary Artery Constriction in the rat
    Cardiovascular research, 1994
    Co-Authors: Harer Huang, Krzysztof Reiss, Leonard G. Meggs, Carl V. Hamby, Piero Anversa
    Abstract:

    Objective: The aim of the study was to determine the effect of Coronary Artery Constriction on the density of angiotensin II receptors and on the effector responses coupled with these receptors on myocytes one week after surgical induction of Coronary Artery stenosis in rats. Methods : After induction of Coronary Artery stenosis and following the estimation of global cardiac performance, myocytes were enzymatically dissociated and radio- ligand binding studies were performed. In addition, the isotonic contractile performance, cytosolic calcium transients. and angiotensin II stimulated inositol phosphate generation in myocytes were measured in the presence and absence of the angiotensin II receptor subtype antagonist losartan. Results: After documenting left ventricular failure and right ventricular dysfunction, the expression and density of angiotensin II receptors in left ventricular niyocytes were evaluated and found to be increased 3.1 -fold and 4.1 -fold, respectively. Corresponding increases in right ventricular myocytes were 3.6-fold and 4.5-fold. In contrast, the quantity of the regulatory protein Gqα was not altered in either ventricle. Angiotensin I1 did not increase the generation of total inositol phosphates in left and right ventricular myocytes at maximum stimulation. However, the threshold for the formation of inositol phosphates was lowered in left ventricular myocytes of Coronary narrowed rats. Measurements of single cell mechanics indicated that angiotensin I1 stimulation markedly improved the depression in myocyte function biventricularly. This inotropic effect was coupled with the restoration of cytosolic calcium. Conclusions : The upregulation of angiotensin I1 receptors on myocytes in this model of global ischaemia may be a compensatory mechanism ameliorating myocyte contractility in an attempt to sustain Ventricular pump function. Cardiovascular Research 1994; 28 :1564-1573

  • Coronary Artery Constriction in rats affects the activation of α1 adrenergic receptors in cardiac myocytes
    Cardiovascular Research, 1994
    Co-Authors: Wei Cheng, Krzysztof Reiss, Joseph M Capasso, Leonard G. Meggs, Carl V. Hamby, Joseph Coupet, Piero Anversa
    Abstract:

    Objective: To determine whether α1 adrenergic receptor mediated myocyte contractility and growth are depressed acutely after non-occlusive Coronary Artery narrowing, the left Coronary Artery was constricted in rats and mechanical behaviour, cytosolic calcium, and regulation of α1 adrenergic receptors were examined in myocytes seven days later. Methods: Coronary Artery stenosis was surgically induced in rats and following the estimation of global cardiac performance myocytes were enzymatically dissociated and radioligand binding studies were performed. In addition, the isotonic contractile performance, cytosolic calcium transients and noradrenaline stimulated inositol phosphate generation in myocytes were measured in the presence of WB 4101 or after chlorethylclonidine treatment. Results: Estimations of cell mechanics in vitro established that peak shortening was decreased by 36% and 18% in left and right ventricular myocytes of Coronary stenosed rats. Time to peak shortening was prolonged by 29% in left and 20% in right myocytes, whereas velocity of shortening was decreased by 27% in left myocytes. These alterations were associated with increases in cell length and width, indicative of myocyte hypertrophy. In addition, Coronary stenosis was accompanied by reductions in the expression of α1a and α1b receptor subtypes in myocytes α1 Adrenergic receptor density and noradrenaline stimulated phosphoinositol turnover were decreased by 30% and 34% in left myocytes. α1 Adrenergic receptor subtype mediated cytosolic calcium concentration and myocyte mechanical performance were also impaired in left myocytes only. The α1a adrenergic receptor subtype antagonist WB 4101 abolished noradrenaline stimulated inositol phosphate generation in myocytes, whereas chlorethylclonidine at large doses only partially inhibited this response. Conclusions: In conclusion, Coronary narrowing leads to defects in the regulation of α1 adrenergic receptors on myocytes which are coupled with attenuation in the transmission of signals, possibly affecting mvocyte cell function and ongoing reactive cellular hypertrophy. Cardiovascular Research 1994; 28: 1070-1082

Alain Nitenberg - One of the best experts on this subject based on the ideXlab platform.

  • cardiovascular outcome of patients with abnormal Coronary vasomotion and normal Coronary arteriography is worse in type 2 diabetes mellitus than in arterial hypertension a 10 year follow up study
    Atherosclerosis, 2005
    Co-Authors: Alain Nitenberg, Isabelle Antony, I Pham, P Valensi, J R Attali, Denis Chemla
    Abstract:

    Diabetes and arterial hypertension are major cardiovascular risk factors. Coronary endothelial dysfunction is frequently observed in diabetic and hypertensive patients. This study was designed to compare cardiovascular outcome of hypertensive (HT) and type 2 diabetic patients (D2) with angiographically normal Coronary arteries on the basis of their epicardial Coronary endothelial function. Coronary reactivity assessment by cold-pressor test (CPT) using quantitative Coronary angiography was achieved in 65 HT (45 males, 20 females) aged 51.9+/-7.6 years, and in 59 D2 (32 males, 27 females) aged 48.9+/-7.3 years, with angiographically normal Coronary arteries and without other major Coronary risk factor. Cardiovascular events (CVE) were recorded with a mean follow-up of 108+/-15 months in HT, and 113+/-10 months in D2. During CPT, in HT Coronary Artery dilation occurred in 10.8% of the patients, no change in 21.5%, and Constriction in 67.7%. In D2, dilation occurred in 3.4% of the patients, no change in 18.6%, and Constriction in 78.0%. During follow-up, in HT there were nine CVE in 6/65 patients (9.2%), all in the 6/44 (13.6%) patients with Coronary Artery Constriction. In D2, there were 18 CVE in 16/59 patients (27.1%, P<0.01 versus HT), with 17 CVE in the 15/46 patients with Coronary Artery Constriction, and one CVE in the 1/13 patients without Constriction (32.6% versus 7.7%). In patients with Coronary Artery Constriction, CVE were more frequent in D2 than in HT (P<0.05). Last, CVE were more severe and occurred earlier in D2 than in HT. In conclusion, epicardial Coronary endothelial dysfunction is predictive of long-term CVE in HT and D2 with angiographically normal Coronary arteries. Cardiovascular outcome of patients with Coronary Constriction is worse in D2 than in HT. At the opposite, patients without Constriction have good cardiovascular prognosis in both subgroups.

  • epicardial Coronary Artery Constriction to cold pressor test is predictive of cardiovascular events in hypertensive patients with angiographically normal Coronary arteries and without other major Coronary risk factor
    Atherosclerosis, 2004
    Co-Authors: Alain Nitenberg, Denis Chemla, Isabelle Antony
    Abstract:

    Epicardial Coronary endothelial dysfunction independently predicts cardiovascular events in patients with Coronary risk factors. This study was designed to evaluate outcome of hypertensive patients on the basis of their epicardial Coronary function assessed by cold pressor test (CPT). Control subjects (n = 68, 48.8 +/- 7.6 years) and hypertensive patients (n = 83, 51.3 +/- 7.9 years) with angiographically normal Coronary arteries and without other major Coronary risk factor underwent epicardial Coronary reactivity assessment to CPT using quantitative angiography. Cardiovascular events were recorded with a mean follow-up of 115 months (range 84-132). In control subjects, dilation occurred in 88.2%, no change in 11.8% (mean diameter change: +14.6 +/- 9.3%). In hypertensive patients, dilation occurred in 13.3%, no change in 25.3% (mean diameter change for both: +10.9 +/- 11.2%), and Constriction in 61.4% (mean diameter change: -12.7 +/- 3.4%). Endothelium-independent dilation was normal in control subjects and hypertensive patients. In control subjects, there were three cardiovascular events in two subjects (2.9%). In hypertensive patients, there were 17 cardiovascular events in 12 patients (14.5%, P < 0.01 versus control subjects), with 15 cardiovascular events in the 10/51 patients (19.6%) with Coronary Artery Constriction, and two cardiovascular events in the 2/32 patients (6.3%) with no change or dilation (P < 0.05). In conclusion, in hypertensive patients with angiographically normal Coronary arteries and without other major Coronary risk factors, epicardial Coronary Artery dysfunction assessed by the cold pressor test is predictive of long-term cardiovascular events.

  • prognostic value of epicardial Coronary Artery Constriction to the cold pressor test in type 2 diabetic patients with angiographically normal Coronary arteries and no other major Coronary risk factors
    Diabetes Care, 2004
    Co-Authors: Alain Nitenberg, P Valensi, J R Attali, Regis Sachs, E Cosson, Isabelle Antony
    Abstract:

    OBJECTIVE —Endothelium-dependent Coronary dilation is impaired in diabetic patients and has been found to independently predict cardiovascular events (CVEs) in patients with multiple Coronary risk factors. The aim of this study was to evaluate the outcome of type 2 diabetic patients on the basis of epicardial Coronary dysfunction. RESEARCH DESIGN AND METHODS — We examined 56 control subjects (aged 51.7 ± 6.4 years) using Coronary Artery response to the cold pressor test (quantitative Coronary angiography) and compared them with 72 type 2 diabetic patients (aged 50.3 ± 8.5 years) without other major Coronary risk factors. RESULTS —Average diameter change was 17.2 ± 10.4% in the control subjects, dilation occurred in 91.1% of subjects, no change occurred in 8.9%, and there was no Constriction. Average diameter change was −14.4 ± 12.1% in diabetic patients ( P P P CONCLUSIONS —In type 2 diabetic patients without other major Coronary risk factors, Constriction of angiographically normal Coronary arteries to the cold pressor test is predictive of long-term CVEs.

  • Coronary Artery Constriction caused by the cold pressor test in human hypertension
    Hypertension, 1994
    Co-Authors: Isabelle Antony, Eduardo Aptecar, Guy Lerebours, Alain Nitenberg
    Abstract:

    Hypertensive patients with angiographically normal Coronary arteries may have myocardial ischemia when metabolic demand increases. Abnormal epicardial Coronary Artery vasomotion in response to sympathetic stimulation may contribute to ischemia in such patients. We studied the vasomotor response of smooth Coronary arteries to a cold pressor test in 10 hypertensive patients without other risk factors and in 9 control subjects. Vessel dimensions were measured by quantitative angiography, and blood flow was calculated using an intraCoronary Doppler catheter in the left anterior descending Coronary Artery. In response to cold pressor stimulation, arteries of control subjects dilated 13.0 +/- 5.9% (P < .001), and they constricted 8.2 +/- 8.5% in hypertensive patients (P < .001). Rate-pressure product increased from 9466 +/- 1677 to 12,547 +/- 2367 beats per minute (bpm).mm Hg in control subjects (P < .001) and from 13,720 +/- 1823 to 17,353 +/- 2037 bpm.mm Hg in hypertensive patients (P < .001). Coronary blood flow velocity and blood flow increased 51 +/- 26% (P < .05) and 87 +/- 27% (P < .001), respectively, in control subjects and 68 +/- 52% (P < .05) and 36 +/- 33% (P < .01) in hypertensive patients. At peak cold pressor test, despite a significant higher rate-pressure product in hypertensive patients, blood flow was similar in both groups, suggesting an uncoupling between myocardial metabolic demand and supply. Thus, hypertension impairs the vasodilator response of angiographically normal Coronary arteries to a cold pressor test. This abnormal response may be due to enhanced catecholamine reactivity and/or impairment of endothelial flow-mediated vasodilator response.

Isabelle Antony - One of the best experts on this subject based on the ideXlab platform.

  • cardiovascular outcome of patients with abnormal Coronary vasomotion and normal Coronary arteriography is worse in type 2 diabetes mellitus than in arterial hypertension a 10 year follow up study
    Atherosclerosis, 2005
    Co-Authors: Alain Nitenberg, Isabelle Antony, I Pham, P Valensi, J R Attali, Denis Chemla
    Abstract:

    Diabetes and arterial hypertension are major cardiovascular risk factors. Coronary endothelial dysfunction is frequently observed in diabetic and hypertensive patients. This study was designed to compare cardiovascular outcome of hypertensive (HT) and type 2 diabetic patients (D2) with angiographically normal Coronary arteries on the basis of their epicardial Coronary endothelial function. Coronary reactivity assessment by cold-pressor test (CPT) using quantitative Coronary angiography was achieved in 65 HT (45 males, 20 females) aged 51.9+/-7.6 years, and in 59 D2 (32 males, 27 females) aged 48.9+/-7.3 years, with angiographically normal Coronary arteries and without other major Coronary risk factor. Cardiovascular events (CVE) were recorded with a mean follow-up of 108+/-15 months in HT, and 113+/-10 months in D2. During CPT, in HT Coronary Artery dilation occurred in 10.8% of the patients, no change in 21.5%, and Constriction in 67.7%. In D2, dilation occurred in 3.4% of the patients, no change in 18.6%, and Constriction in 78.0%. During follow-up, in HT there were nine CVE in 6/65 patients (9.2%), all in the 6/44 (13.6%) patients with Coronary Artery Constriction. In D2, there were 18 CVE in 16/59 patients (27.1%, P<0.01 versus HT), with 17 CVE in the 15/46 patients with Coronary Artery Constriction, and one CVE in the 1/13 patients without Constriction (32.6% versus 7.7%). In patients with Coronary Artery Constriction, CVE were more frequent in D2 than in HT (P<0.05). Last, CVE were more severe and occurred earlier in D2 than in HT. In conclusion, epicardial Coronary endothelial dysfunction is predictive of long-term CVE in HT and D2 with angiographically normal Coronary arteries. Cardiovascular outcome of patients with Coronary Constriction is worse in D2 than in HT. At the opposite, patients without Constriction have good cardiovascular prognosis in both subgroups.

  • epicardial Coronary Artery Constriction to cold pressor test is predictive of cardiovascular events in hypertensive patients with angiographically normal Coronary arteries and without other major Coronary risk factor
    Atherosclerosis, 2004
    Co-Authors: Alain Nitenberg, Denis Chemla, Isabelle Antony
    Abstract:

    Epicardial Coronary endothelial dysfunction independently predicts cardiovascular events in patients with Coronary risk factors. This study was designed to evaluate outcome of hypertensive patients on the basis of their epicardial Coronary function assessed by cold pressor test (CPT). Control subjects (n = 68, 48.8 +/- 7.6 years) and hypertensive patients (n = 83, 51.3 +/- 7.9 years) with angiographically normal Coronary arteries and without other major Coronary risk factor underwent epicardial Coronary reactivity assessment to CPT using quantitative angiography. Cardiovascular events were recorded with a mean follow-up of 115 months (range 84-132). In control subjects, dilation occurred in 88.2%, no change in 11.8% (mean diameter change: +14.6 +/- 9.3%). In hypertensive patients, dilation occurred in 13.3%, no change in 25.3% (mean diameter change for both: +10.9 +/- 11.2%), and Constriction in 61.4% (mean diameter change: -12.7 +/- 3.4%). Endothelium-independent dilation was normal in control subjects and hypertensive patients. In control subjects, there were three cardiovascular events in two subjects (2.9%). In hypertensive patients, there were 17 cardiovascular events in 12 patients (14.5%, P < 0.01 versus control subjects), with 15 cardiovascular events in the 10/51 patients (19.6%) with Coronary Artery Constriction, and two cardiovascular events in the 2/32 patients (6.3%) with no change or dilation (P < 0.05). In conclusion, in hypertensive patients with angiographically normal Coronary arteries and without other major Coronary risk factors, epicardial Coronary Artery dysfunction assessed by the cold pressor test is predictive of long-term cardiovascular events.

  • prognostic value of epicardial Coronary Artery Constriction to the cold pressor test in type 2 diabetic patients with angiographically normal Coronary arteries and no other major Coronary risk factors
    Diabetes Care, 2004
    Co-Authors: Alain Nitenberg, P Valensi, J R Attali, Regis Sachs, E Cosson, Isabelle Antony
    Abstract:

    OBJECTIVE —Endothelium-dependent Coronary dilation is impaired in diabetic patients and has been found to independently predict cardiovascular events (CVEs) in patients with multiple Coronary risk factors. The aim of this study was to evaluate the outcome of type 2 diabetic patients on the basis of epicardial Coronary dysfunction. RESEARCH DESIGN AND METHODS — We examined 56 control subjects (aged 51.7 ± 6.4 years) using Coronary Artery response to the cold pressor test (quantitative Coronary angiography) and compared them with 72 type 2 diabetic patients (aged 50.3 ± 8.5 years) without other major Coronary risk factors. RESULTS —Average diameter change was 17.2 ± 10.4% in the control subjects, dilation occurred in 91.1% of subjects, no change occurred in 8.9%, and there was no Constriction. Average diameter change was −14.4 ± 12.1% in diabetic patients ( P P P CONCLUSIONS —In type 2 diabetic patients without other major Coronary risk factors, Constriction of angiographically normal Coronary arteries to the cold pressor test is predictive of long-term CVEs.

  • Coronary Artery Constriction caused by the cold pressor test in human hypertension
    Hypertension, 1994
    Co-Authors: Isabelle Antony, Eduardo Aptecar, Guy Lerebours, Alain Nitenberg
    Abstract:

    Hypertensive patients with angiographically normal Coronary arteries may have myocardial ischemia when metabolic demand increases. Abnormal epicardial Coronary Artery vasomotion in response to sympathetic stimulation may contribute to ischemia in such patients. We studied the vasomotor response of smooth Coronary arteries to a cold pressor test in 10 hypertensive patients without other risk factors and in 9 control subjects. Vessel dimensions were measured by quantitative angiography, and blood flow was calculated using an intraCoronary Doppler catheter in the left anterior descending Coronary Artery. In response to cold pressor stimulation, arteries of control subjects dilated 13.0 +/- 5.9% (P < .001), and they constricted 8.2 +/- 8.5% in hypertensive patients (P < .001). Rate-pressure product increased from 9466 +/- 1677 to 12,547 +/- 2367 beats per minute (bpm).mm Hg in control subjects (P < .001) and from 13,720 +/- 1823 to 17,353 +/- 2037 bpm.mm Hg in hypertensive patients (P < .001). Coronary blood flow velocity and blood flow increased 51 +/- 26% (P < .05) and 87 +/- 27% (P < .001), respectively, in control subjects and 68 +/- 52% (P < .05) and 36 +/- 33% (P < .01) in hypertensive patients. At peak cold pressor test, despite a significant higher rate-pressure product in hypertensive patients, blood flow was similar in both groups, suggesting an uncoupling between myocardial metabolic demand and supply. Thus, hypertension impairs the vasodilator response of angiographically normal Coronary arteries to a cold pressor test. This abnormal response may be due to enhanced catecholamine reactivity and/or impairment of endothelial flow-mediated vasodilator response.

Denis Chemla - One of the best experts on this subject based on the ideXlab platform.

  • cardiovascular outcome of patients with abnormal Coronary vasomotion and normal Coronary arteriography is worse in type 2 diabetes mellitus than in arterial hypertension a 10 year follow up study
    Atherosclerosis, 2005
    Co-Authors: Alain Nitenberg, Isabelle Antony, I Pham, P Valensi, J R Attali, Denis Chemla
    Abstract:

    Diabetes and arterial hypertension are major cardiovascular risk factors. Coronary endothelial dysfunction is frequently observed in diabetic and hypertensive patients. This study was designed to compare cardiovascular outcome of hypertensive (HT) and type 2 diabetic patients (D2) with angiographically normal Coronary arteries on the basis of their epicardial Coronary endothelial function. Coronary reactivity assessment by cold-pressor test (CPT) using quantitative Coronary angiography was achieved in 65 HT (45 males, 20 females) aged 51.9+/-7.6 years, and in 59 D2 (32 males, 27 females) aged 48.9+/-7.3 years, with angiographically normal Coronary arteries and without other major Coronary risk factor. Cardiovascular events (CVE) were recorded with a mean follow-up of 108+/-15 months in HT, and 113+/-10 months in D2. During CPT, in HT Coronary Artery dilation occurred in 10.8% of the patients, no change in 21.5%, and Constriction in 67.7%. In D2, dilation occurred in 3.4% of the patients, no change in 18.6%, and Constriction in 78.0%. During follow-up, in HT there were nine CVE in 6/65 patients (9.2%), all in the 6/44 (13.6%) patients with Coronary Artery Constriction. In D2, there were 18 CVE in 16/59 patients (27.1%, P<0.01 versus HT), with 17 CVE in the 15/46 patients with Coronary Artery Constriction, and one CVE in the 1/13 patients without Constriction (32.6% versus 7.7%). In patients with Coronary Artery Constriction, CVE were more frequent in D2 than in HT (P<0.05). Last, CVE were more severe and occurred earlier in D2 than in HT. In conclusion, epicardial Coronary endothelial dysfunction is predictive of long-term CVE in HT and D2 with angiographically normal Coronary arteries. Cardiovascular outcome of patients with Coronary Constriction is worse in D2 than in HT. At the opposite, patients without Constriction have good cardiovascular prognosis in both subgroups.

  • epicardial Coronary Artery Constriction to cold pressor test is predictive of cardiovascular events in hypertensive patients with angiographically normal Coronary arteries and without other major Coronary risk factor
    Atherosclerosis, 2004
    Co-Authors: Alain Nitenberg, Denis Chemla, Isabelle Antony
    Abstract:

    Epicardial Coronary endothelial dysfunction independently predicts cardiovascular events in patients with Coronary risk factors. This study was designed to evaluate outcome of hypertensive patients on the basis of their epicardial Coronary function assessed by cold pressor test (CPT). Control subjects (n = 68, 48.8 +/- 7.6 years) and hypertensive patients (n = 83, 51.3 +/- 7.9 years) with angiographically normal Coronary arteries and without other major Coronary risk factor underwent epicardial Coronary reactivity assessment to CPT using quantitative angiography. Cardiovascular events were recorded with a mean follow-up of 115 months (range 84-132). In control subjects, dilation occurred in 88.2%, no change in 11.8% (mean diameter change: +14.6 +/- 9.3%). In hypertensive patients, dilation occurred in 13.3%, no change in 25.3% (mean diameter change for both: +10.9 +/- 11.2%), and Constriction in 61.4% (mean diameter change: -12.7 +/- 3.4%). Endothelium-independent dilation was normal in control subjects and hypertensive patients. In control subjects, there were three cardiovascular events in two subjects (2.9%). In hypertensive patients, there were 17 cardiovascular events in 12 patients (14.5%, P < 0.01 versus control subjects), with 15 cardiovascular events in the 10/51 patients (19.6%) with Coronary Artery Constriction, and two cardiovascular events in the 2/32 patients (6.3%) with no change or dilation (P < 0.05). In conclusion, in hypertensive patients with angiographically normal Coronary arteries and without other major Coronary risk factors, epicardial Coronary Artery dysfunction assessed by the cold pressor test is predictive of long-term cardiovascular events.

Jan Kajstura - One of the best experts on this subject based on the ideXlab platform.

  • insulin like growth factor 1 attenuates the detrimental impact of nonocclusive Coronary Artery Constriction on the heart
    Circulation Research, 1999
    Co-Authors: Manabu Setoguchi, Jan Kajstura, Annarosa Leri, Xiaowei Wang, Anna Maria Andreoli, Ashwani Malhotra, Piero Anversa
    Abstract:

    Coronary Artery narrowing (CAN) induces tissue injury, which may involve myocyte necrosis and apoptosis. Insulin-like growth factor (IGF)-1 may counteract cell death, modifying the detrimental effects of myocardial ischemia. On this basis, CAN was produced in female FVB.Igf+/- mice and nontransgenic littermates, and the animals were euthanized 7 days later. CAN consisted of an 82% reduction in the vessel luminal cross-sectional area in both groups of mice. Severe left ventricular dysfunction was present in CAN nontransgenic and transgenic mice, but heart and left ventricular weights increased more in littermates than in FVB.Igf+/- mice. Similarly, the changes in chamber volume and diastolic wall stress were greater in nontransgenic mice. Subacute tissue injury, represented by foci of replacement fibrosis, was 2.6-fold higher in CAN littermates than in FVB.Igf+/- mice. Ongoing myocyte necrosis was 5-fold greater in nontransgenic mice, whereas apoptosis was low and did not differ in the 2 groups of mice. In CAN nontransgenic mice, myocyte necrosis was 12-fold more frequent than apoptosis but, in CAN transgenic mice, these 2 types of cell death were comparable. alpha-Myosin and beta-myosin isoform mRNAs were affected by CAN, but alpha-myosin mRNA was reduced more in nontransgenic mice. In conclusion, myocyte necrosis and replacement fibrosis are the prevailing forms of myocardial damage induced by CAN. Constitutive overexpression of IGF-1 attenuates myocyte necrosis and tissue injury, having no effect on cell apoptosis. These factors limit ventricular dilation, myocardial loading, cardiac hypertrophy, and alterations in alpha- and beta-myosin isoform expression.

  • Coronary Artery Constriction in rats: necrotic and apoptotic myocyte death.
    The American Journal of Cardiology, 1998
    Co-Authors: Jan Kajstura, Giorgio Olivetti, Yu Liu, Alessandra Baldini, Annarosa Leri, Piero Anversa
    Abstract:

    The purpose of this study was to determine whether Coronary Artery narrowing was associated with the activation of necrotic and apoptotic myocyte cell death in the myocardium and whether these 2 forms of cell death were restricted to the left ventricle, or involved the other portions of the heart. Coronary Artery narrowing was surgically induced in rats, and the animals were killed from 45 minutes to 12 days after surgery. Myocyte apoptosis was detected by the terminal deoxynucleotidyl transferase assay, confocal microscopy, and deoxyribonucleic acid (DNA) agarose gel electrophoresis. Myocyte necrosis was identified by myosin monoclonal antibody labeling of the cytoplasm. A separate group of animals was treated with trimetazidine in an attempt to interfere with tissue injury. Coronary Artery narrowing was characterized by myocyte apoptosis in the left ventricle and interventricular septum, which progressively increased from 45 minutes to 6 days. However, apoptosis was not observed at 12 days. Conversely, myocyte necrosis reached its maximum value at 1 day and was still present at 12 days. This form of cell death affected not only the left ventricular free wall and interventricular septum, but also the right ventricle. Cell necrosis markedly exceeded apoptosis at all intervals. At the peak of cell death, myocyte necrosis was 52-fold and 33-fold higher than apoptosis in the left ventricle and septum. In conclusion, necrotic myocyte cell death is the prevailing form of damage produced by Coronary Artery narrowing, but apoptotic cell death contributes to the loss of myocytes in the ischemic heart. Trimetazidine treatment attenuated the extent of myocardial damage produced by global ischemia.

  • Ventricular Remodeling Following Coronary Artery Constriction and Hypertension
    Developments in Cardiovascular Medicine, 1996
    Co-Authors: Piero Anversa, Krzysztof Reiss, Jan Kajstura, Giorgio Olivetti, Xun Zhang, Federico Quaini, Edmund H. Sonnenblick
    Abstract:

    In Coronary Artery disease in humans, the severity of the atherosclerotic involvement of the Coronary circulation frequently does not correlate with the impairment in cardiac pump performance, and therefore anatomic condition is a poor predictor of clinical outcome and mortality of the patient population [1–4]. Based on acute studies in animal models [5], the conclusion has been reached that severe reductions in Coronary Artery diameter of nearly 80% are required to create an imbalance between oxygen demand and supply, possibly leading to scattered myocardial damage and the initiation of ischemic cardiomyopathy. However, it has recently been shown that Coronary Artery Constriction of moderate degree may induce diffuse myocytolytic necrosis and marked alterations in ventricular hemodynamics [6]. Moreover, the phenomenon of myocyte cell death was documented to persist with time, chronically affecting the functional and anatomical characteristics of the heart [7,8]. Thus, modest decreases in Coronary diameter may have clinical implications that have not been previously appreciated, and untreated Coronary Artery narrowing may progressively affect the structural integrity of the myocardium.

  • Impairment of myocyte contractility following Coronary Artery narrowing is associated with activation of the myocyte IGF1 autocrine system, enhanced expression of late growth related genes, DNA synthesis, and myocyte nuclear mitotic division in rats.
    Experimental cell research, 1993
    Co-Authors: Krzysztof Reiss, Jan Kajstura, Joseph M Capasso, Thomas A. Marino, Piero Anversa
    Abstract:

    To determine whether the alterations in ventricular loading and myocyte cellular contractile performance produced by short-term Coronary Artery Constriction were associated with the activation of genes implicated in myocyte DNA synthesis including changes in the expression of insulin-like growth factor-1 (IGF1) and insulin-like growth factor-1 receptors (IGF1-R), nonocclusive Coronary Artery narrowing (CAN) was induced in rats. Animals were examined 2 and 7 days after Coronary Constriction. Following the in vivo documentation of severe impairment of ventricular performance, estimations of single-cell mechanics in vitro showed that peak shortening was decreased in left and right myocytes of Coronary stenosed rats. Moreover, time to peak shortening was prolonged whereas velocity of shortening was decreased. These defects in myocyte contractility were accompanied by increases in cell length and width, indicative of myocyte enlargement biventricularly. In addition, CAN led to an enhanced expression of proliferating cell nuclear antigen (PCNA) and histone-H3 genes in myocytes at 2 and 7 days after surgery. PCNA protein was also detected in these stressed cells. These molecular responses were associated with increases in mRNA for IGF1 and IGF1-R in combination with enhanced DNA synthesis and appearance of myocyte nuclear mitotic division. In conclusion, cardiac myocytes may respond to the elevation in wall and myocyte stress by activating an IGF1-IGF1-R autocrine system which may modulate the induction of late growth related genes which are essential for DNA replication and myocyte cellular hyperplasia.