The Experts below are selected from a list of 222 Experts worldwide ranked by ideXlab platform
Charles E Murry - One of the best experts on this subject based on the ideXlab platform.
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fibroblast growth factor 2 regulates Myocardial Infarct repair effects on cell proliferation scar contraction and ventricular function
American Journal of Pathology, 2007Co-Authors: Jitka A I Virag, Marsha L Rolle, Julia Reece, Sandrine N Hardouin, Eric O Feigl, Charles E MurryAbstract:Fibroblast growth factor-2 (FGF2, bFGF) has been proposed to regulate wound healing and angiogenesis, but skin wound healing in FGF2-knockout (FGF2-KO) animals is only slightly delayed. To determine the role of FGF2 in Myocardial Infarct repair, we studied the evolution of left ventricular geometry, cell proliferation, matrix content, and cardiac function in mice lacking or overexpressing (FGF2-Tg) FGF2. Despite having no effect on initial Infarct size, deletion of FGF2 resulted in reduced fibroblast proliferation and interstitial collagen deposition, decreased endothelial proliferation and vascular density, and decreased cardiomyocyte hypertrophy. Furthermore, FGF2-KO mice demonstrated a complete absence of scar contraction, resulting in increased final Infarct size and marked increases in chamber size and Infarct expansion. These deficits ultimately impaired left ventricular dP/dt compared with wild-type Infarcted mice. Conversely, overexpression of FGF2 increased fibroblast proliferation and collagen deposition, accelerated endothelial proliferation, and enhanced cardiomyocyte hypertrophy after Infarction. These changes curbed Infarct expansion and preserved left ventricular function. Thus, FGF2 is an important regulator of cell proliferation, angiogenesis, collagen synthesis, myocyte hypertrophy, scar contraction, and, ultimately, left ventricular contractile function during Infarct repair. FGF2 may be more important in healing of Infarcts compared with skin wounds because of the mechanical stress under which Infarcts heal.
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myofibroblast and endothelial cell proliferation during murine Myocardial Infarct repair
American Journal of Pathology, 2003Co-Authors: Jitka A I Virag, Charles E MurryAbstract:Granulation tissue formation is a critical step in Infarct repair, however, the kinetics of cell replication and the molecules that regulate this process are poorly understood. In uninjured mouse hearts and at 2 days post-Infarction, very little DNA synthesis (measured by incorporation of a BrdU pulse) was detected in any cell type. Four days after permanent coronary occlusion, the rates of myofibroblast (smooth muscle α-actin and BrdU double-positive) and endothelial cell (CD31 and BrdU double-positive) proliferation were 15.4 ± 1.1% and 2.9 ± 0.5%, respectively. Most proliferating cells were located at the interface of the Infarct and viable tissue. By 1 week, fibroblast and endothelial cell proliferation declined to 4.1 ± 0.6% and 0.7 ± 0.1%, respectively. In the 2-week Infarct, the remaining necrosis had been phagocytosed, and fibroblast and endothelial cell proliferation were 2 ) declined from 3643 ± 82 in control hearts to 2716 ± 197 at 1 week and 1010 ± 47 at 4 weeks post-Myocardial Infarction (MI). The average percent area occupied by vessels did not change significantly between the groups but the area/vessel (μm 2 ) increased from 14.1 ± 0.3 in control hearts to 16.9 ± 1.9 at 1 week and 38.7 ± 7.9 at 4 weeks post-MI. These data indicate that mitogens for fibroblasts and endothelial cells peak within 4 days of Infarction in the mouse heart. This provides the basis for identifying the responsible molecules and developing strategies to alter wound repair and improve cardiac function.
Balazs Ruzsics - One of the best experts on this subject based on the ideXlab platform.
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Novel MRI and CT Approaches for the Characterization of Myocardial Infarct
Current Radiology Reports, 2013Co-Authors: Sukumaran Binukrishnan, Vishal Sharma, Abishek Kumar, Carlo Nicola Cecco, U. Joseph Schoepf, Balazs RuzsicsAbstract:Accurate Myocardial viability assessment is essential to optimize revascularization and/or medical treatment in patients with Myocardial Infarct. To date, cardiac magnetic resonance imaging (MRI) is the widely accepted clinical standard for visualization, characterization and quantification of Myocardial viability. Multidetector computed tomography (CT) is reported by numerous authors as an emerging imaging modality for Myocardial viability assessment. This review article summarizes cardiac MRI and CT modalities for Myocardial viability assessment.
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Differentiation of acute and four-week old Myocardial Infarct with Gd(ABE-DTTA)-enhanced CMR.
Journal of Cardiovascular Magnetic Resonance, 2010Co-Authors: Robert Kirschner, Levente Tóth, Akos Varga-szemes, Tamás Simor, Pal Suranyi, Pál Kiss, Balazs Ruzsics, Attila Tóth, Robert A. Baker, Brigitta C. BrottAbstract:Background Standard extracellular cardiovascular magnetic resonance (CMR) contrast agents (CA) do not provide differentiation between acute and older Myocardial Infarcts (MI). The purpose of this study was to develop a method for differentiation between acute and older Myocardial Infarct using Myocardial late-enhancement (LE) CMR by a new, low molecular weight contrast agent. Dogs (n = 6) were studied in a closed-chest, reperfused, double Myocardial Infarct model. Myocardial Infarcts were generated by occluding the Left Anterior Descending (LAD) coronary artery with an angioplasty balloon for 180 min, and four weeks later occluding the Left Circumflex (LCx) coronary artery for 180 min. LE images were obtained on day 3 and day 4 after second Myocardial Infarct, using Gd(DTPA) (standard extracellular contrast agent) and Gd(ABE-DTTA) (new, low molecular weight contrast agent), respectively. Triphenyltetrazolium chloride (TTC) histomorphometry validated existence and location of Infarcts. Hematoxylin-eosin and Masson's trichrome staining provided histologic evaluation of Infarcts.
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Myocardial Infarct with Gd(ABE-DTTA)-enhanced CMR
2010Co-Authors: Robert Kirschner, Levente Tóth, Akos Varga-szemes, Tamás Simor, Pal Suranyi, Pál Kiss, Balazs Ruzsics, Attila Tóth, Robert L. Baker, Brigitta C. BrottAbstract:Background: Standard extracellular cardiovascular magnetic resonance (CMR) contrast agents (CA) do not provide differentiation between acute and older Myocardial Infarcts (MI). The purpose of this study was to develop a method for differentiation between acute and older Myocardial Infarct using Myocardial late-enhancement (LE) CMR by a new, low molecular weight contrast agent. Dogs (n = 6) were studied in a closed-chest, reperfused, double Myocardial Infarct model. Myocardial Infarcts were generated by occluding the Left Anterior Descending (LAD) coronary artery with an angioplasty balloon for 180 min, and four weeks later occluding the Left Circumflex (LCx) coronary artery for 180 min. LE images were obtained on day 3 and day 4 after second Myocardial Infarct, using Gd(DTPA) (standard extracellular contrast agent) and Gd(ABEDTTA) (new, low molecular weight contrast agent), respectively. Triphenyltetrazolium chloride (TTC) histomorphometry validated existence and location of Infarcts. Hematoxylin-eosin and Masson's trichrome staining provided histologic evaluation of Infarcts. Results: Gd(ABE-DTTA) or Gd(DTPA) highlighted the acute Infarct, whereas the four-week old Infarct was visualized by Gd(DTPA), but not by Gd(ABE-DTTA). With Gd(ABE-DTTA), the mean ± SD signal intensity enhancement (SIE) was 366 ± 166% and 24 ± 59% in the acute Infarct and the four-week old Infarct, respectively (P < 0.05). The latter did not differ significantly from signal intensity in healthy myocardium (P = NS). Gd(DTPA) produced signal intensity enhancements which were similar in acute (431 ± 124%) and four-week old Infarcts (400 ± 124%, P = NS), and not statistically different from the Gd(ABE-DTTA)-induced SIE in acute Infarct. The existence and localization of both Infarcts were confirmed by triphenyltetrazolium chloride (TTC). Histologic evaluation demonstrated coagulation necrosis, inflammation, and multiple foci of calcification in the four day old Infarct, while the late subacute Infarct showed granulation tissue and early collagen deposition. Conclusions: Late enhancement CMR with separate administrations of standard extracellular contrast agent, Gd(DTPA), and the new low molecular weight contrast agent, Gd(ABE-DTTA), differentiates between acute and late subacute Infarct in a reperfused, double Infarct, canine model.
Jitka A I Virag - One of the best experts on this subject based on the ideXlab platform.
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fibroblast growth factor 2 regulates Myocardial Infarct repair effects on cell proliferation scar contraction and ventricular function
American Journal of Pathology, 2007Co-Authors: Jitka A I Virag, Marsha L Rolle, Julia Reece, Sandrine N Hardouin, Eric O Feigl, Charles E MurryAbstract:Fibroblast growth factor-2 (FGF2, bFGF) has been proposed to regulate wound healing and angiogenesis, but skin wound healing in FGF2-knockout (FGF2-KO) animals is only slightly delayed. To determine the role of FGF2 in Myocardial Infarct repair, we studied the evolution of left ventricular geometry, cell proliferation, matrix content, and cardiac function in mice lacking or overexpressing (FGF2-Tg) FGF2. Despite having no effect on initial Infarct size, deletion of FGF2 resulted in reduced fibroblast proliferation and interstitial collagen deposition, decreased endothelial proliferation and vascular density, and decreased cardiomyocyte hypertrophy. Furthermore, FGF2-KO mice demonstrated a complete absence of scar contraction, resulting in increased final Infarct size and marked increases in chamber size and Infarct expansion. These deficits ultimately impaired left ventricular dP/dt compared with wild-type Infarcted mice. Conversely, overexpression of FGF2 increased fibroblast proliferation and collagen deposition, accelerated endothelial proliferation, and enhanced cardiomyocyte hypertrophy after Infarction. These changes curbed Infarct expansion and preserved left ventricular function. Thus, FGF2 is an important regulator of cell proliferation, angiogenesis, collagen synthesis, myocyte hypertrophy, scar contraction, and, ultimately, left ventricular contractile function during Infarct repair. FGF2 may be more important in healing of Infarcts compared with skin wounds because of the mechanical stress under which Infarcts heal.
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myofibroblast and endothelial cell proliferation during murine Myocardial Infarct repair
American Journal of Pathology, 2003Co-Authors: Jitka A I Virag, Charles E MurryAbstract:Granulation tissue formation is a critical step in Infarct repair, however, the kinetics of cell replication and the molecules that regulate this process are poorly understood. In uninjured mouse hearts and at 2 days post-Infarction, very little DNA synthesis (measured by incorporation of a BrdU pulse) was detected in any cell type. Four days after permanent coronary occlusion, the rates of myofibroblast (smooth muscle α-actin and BrdU double-positive) and endothelial cell (CD31 and BrdU double-positive) proliferation were 15.4 ± 1.1% and 2.9 ± 0.5%, respectively. Most proliferating cells were located at the interface of the Infarct and viable tissue. By 1 week, fibroblast and endothelial cell proliferation declined to 4.1 ± 0.6% and 0.7 ± 0.1%, respectively. In the 2-week Infarct, the remaining necrosis had been phagocytosed, and fibroblast and endothelial cell proliferation were 2 ) declined from 3643 ± 82 in control hearts to 2716 ± 197 at 1 week and 1010 ± 47 at 4 weeks post-Myocardial Infarction (MI). The average percent area occupied by vessels did not change significantly between the groups but the area/vessel (μm 2 ) increased from 14.1 ± 0.3 in control hearts to 16.9 ± 1.9 at 1 week and 38.7 ± 7.9 at 4 weeks post-MI. These data indicate that mitogens for fibroblasts and endothelial cells peak within 4 days of Infarction in the mouse heart. This provides the basis for identifying the responsible molecules and developing strategies to alter wound repair and improve cardiac function.
Andreas Dendorfer - One of the best experts on this subject based on the ideXlab platform.
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apstatin a selective inhibitor of aminopeptidase p reduces Myocardial Infarct size by a kinin dependent pathway
British Journal of Pharmacology, 2001Co-Authors: Sebastian Wolfrum, Gabriele Richardt, Peter Dominiak, Hugo A. Katus, Andreas DendorferAbstract:Inhibitors of the angiotensin converting enzyme (ACE) have been shown to exert their cardioprotective actions through a kinin-dependent mechanism. ACE is not the only kinin degrading enzyme in the rat heart. Since aminopeptidase P (APP) has been shown to participate in Myocardial kinin metabolism to the same extent as ACE, the aims of the present study were to investigate whether (a) inhibition of APP leads to a reduction of Myocardial Infarct size in a rat model of acute ischaemia and reperfusion, (b) reduction of Infarct size is mediated by bradykinin, and (c) a combination of APP and ACE inhibition leads to a more pronounced effect than APP inhibition alone. Pentobarbital-anaesthetized rats were subjected to 30 min left coronary artery occlusion followed by 3 h reperfusion. The APP inhibitor apstatin, the ACE-inhibitor ramiprilat, or their combination were administered 5 min before ischaemia. Rats receiving HOE140, a specific B2 receptor antagonist, were pretreated 5 min prior to enzyme inhibitors. Myocardial Infarct size (IS) was determined by tetrazolium staining and expressed as percentage of the area at risk (AAR). IS/AAR% was significantly reduced in rats that received apstatin (18±2%), ramiprilat (18±3%), or apstatin plus ramiprilat (20±4%) as compared with those receiving saline (40±2%), HOE (43±3%) or apstatin plus HOE140 (49±4%). Apstatin reduces IS in an in vivo model of acute Myocardial ischaemia and reperfusion to the same extent than ramiprilat. Cardioprotection achieved by this selective inhibitor of APP is mediated by bradykinin. Combined inhibition of APP and ACE did not result in a more pronounced reduction of IS than APP-inhibition alone. British Journal of Pharmacology (2001) 134, 370–374; doi:10.1038/sj.bjp.0704236
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Apstatin, a selective inhibitor of aminopeptidase P, reduces Myocardial Infarct size by a kinin‐dependent pathway
British Journal of Pharmacology, 2001Co-Authors: Sebastian Wolfrum, Gabriele Richardt, Peter Dominiak, Hugo A. Katus, Andreas DendorferAbstract:Inhibitors of the angiotensin converting enzyme (ACE) have been shown to exert their cardioprotective actions through a kinin-dependent mechanism. ACE is not the only kinin degrading enzyme in the rat heart. Since aminopeptidase P (APP) has been shown to participate in Myocardial kinin metabolism to the same extent as ACE, the aims of the present study were to investigate whether (a) inhibition of APP leads to a reduction of Myocardial Infarct size in a rat model of acute ischaemia and reperfusion, (b) reduction of Infarct size is mediated by bradykinin, and (c) a combination of APP and ACE inhibition leads to a more pronounced effect than APP inhibition alone. Pentobarbital-anaesthetized rats were subjected to 30 min left coronary artery occlusion followed by 3 h reperfusion. The APP inhibitor apstatin, the ACE-inhibitor ramiprilat, or their combination were administered 5 min before ischaemia. Rats receiving HOE140, a specific B2 receptor antagonist, were pretreated 5 min prior to enzyme inhibitors. Myocardial Infarct size (IS) was determined by tetrazolium staining and expressed as percentage of the area at risk (AAR). IS/AAR% was significantly reduced in rats that received apstatin (18±2%), ramiprilat (18±3%), or apstatin plus ramiprilat (20±4%) as compared with those receiving saline (40±2%), HOE (43±3%) or apstatin plus HOE140 (49±4%). Apstatin reduces IS in an in vivo model of acute Myocardial ischaemia and reperfusion to the same extent than ramiprilat. Cardioprotection achieved by this selective inhibitor of APP is mediated by bradykinin. Combined inhibition of APP and ACE did not result in a more pronounced reduction of IS than APP-inhibition alone. British Journal of Pharmacology (2001) 134, 370–374; doi:10.1038/sj.bjp.0704236
Bradley J Martin - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stem cell implantation in a swine Myocardial Infarct model engraftment and functional effects
The Annals of Thoracic Surgery, 2002Co-Authors: Jay G Shake, Peter J Gruber, William A Baumgartner, Guylaine Senechal, Jennifer Meyers, Mark J Redmond, Mark F Pittenger, Bradley J MartinAbstract:Abstract Background . A novel therapeutic option for the treatment of acute Myocardial Infarction involves the use of mesenchymal stem cells (MSCs). The purpose of this study was to investigate whether implantation of autologous MSCs results in sustained engraftment, myogenic differentiation, and improved cardiac function in a swine Myocardial Infarct model. Methods . MSCs were isolated and expanded from bone marrow aspirates of 14 domestic swine. A 60-minute left anterior descending artery occlusion was used to produce anterior wall Infarction. Piezoelectric crystals were placed within the ischemic region for measurement of regional wall thickness and contractile function. Two weeks later animals autologous, Di-I–labeled MSCs (6 × 10 7 ) were implanted into the Infarct by direct injection. Hemodynamic and functional measurements were obtained weekly until the time of sacrifice. Immunohistochemistry was used to assess MSC engraftment and myogenic differentiation. Results . Microscopic analysis showed robust engraftment of MSCs in all treated animals. Expression of muscle-specific proteins was seen as early as 2 weeks and could be identified in all animals at sacrifice. The degree of contractile dysfunction was significantly attenuated at 4 weeks in animals implanted with MSCs (5.4% ± 2.2% versus −3.37% ± 2.7% in control). In addition, the extent of wall thinning after Myocardial Infarction was markedly reduced in treated animals. Conclusions . Mesenchymal stem cells are capable of engraftment in host myocardium, demonstrate expression of muscle specific proteins, and may attenuate contractile dysfunction and pathologic thinning in this model of left ventricular wall Infarction. MSC cardiomyoplasty may have significant clinical potential in attenuating the pathology associated with Myocardial Infarction.
