The role of TGF-β signaling in myocardial infarction and cardiac remodeling

Bujak, Marcin; Frangogiannis, Nikolaos G.

doi:10.1016/j.cardiores.2006.10.002

Cited by 855 publications

(738 citation statements)

References 95 publications

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“…Several pieces of evidence have implicated the TGF-␤ system as a major etiological agent in the pathogenesis of cardiac fibrosis, including type III collagen overexpression and LV remodeling in AMI. 8,35,36 Because latent TGF-␤ can be activated in vitro on oxidative stress generation, 39 anti-oxidative properties of PEDF could contribute directly to its antifibrotic effects in our AMI model as well.…”

Section: Discussionmentioning

confidence: 97%

Administration of Pigment Epithelium-Derived Factor Inhibits Left Ventricular Remodeling and Improves Cardiac Function in Rats with Acute Myocardial Infarction

Ueda

Yamagishi

Matsui

et al. 2011

The American Journal of Pathology

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Oxidative stress and inflammation are involved in cardiac remodeling after acute myocardial infarction (AMI). We have found that pigment epithelium-derived factor (PEDF) inhibits vascular inflammation through its anti-oxidative properties. However, effects of PEDF on cardiac remodeling after AMI remain unknown. We investigated whether PEDF could inhibit left ventricular remodeling and improve cardiac function in rats with AMI. AMI was induced in 8-weekold Sprague-Dawley rats by ligation of the left ascending coronary artery. Rats were treated intravenously with vehicle or 10 g PEDF/100 g b.wt. every day for up to 2 weeks after AMI. Each rat was followed until 16 weeks of age. PEDF levels in infarcted areas and serum were significantly decreased at 1 week after AMI and remained low during the observational periods. PEDF administration inhibited apoptotic cell death and oxidative stress generation around the infarcted areas at 2 and 8 weeks after AMI. Further, PEDF injection suppressed cardiac fibrosis by reducing transforming growth factor-␤ and type III collagen expression, improved left ventricular ejection fraction, ameliorated diastolic dysfunction, and inhibited the increase in left ventricular mass index at 8 weeks after AMI. The present study demonstrated that PEDF could inhibit tissue remodeling and improve cardiac function in AMI rats. Substitution of PEDF may be a novel therapeutic strategy for cardiac remodeling after AMI.

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Section: Discussionmentioning

confidence: 97%

Administration of Pigment Epithelium-Derived Factor Inhibits Left Ventricular Remodeling and Improves Cardiac Function in Rats with Acute Myocardial Infarction

Ueda

Yamagishi

Matsui

et al. 2011

The American Journal of Pathology

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“…TGF-β in the heart stimulates myofibroblasts to produce collagen to replace dead cardiomyocytes (31,32). After S. pneumoniae had induced necroptosis in the heart, de novo collagen deposition was detected in the left ventricle and septum evident by picosirus red staining ( Fig.…”

Section: Cardiac Fibrosismentioning

confidence: 98%

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

Reyes

Restrepo

Hinojosa

et al. 2017

Am J Respir Crit Care Med

117

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“…Through its pleiotropic effects, TGF-β is ideally suited as a key mediator in the transition from inflammation to fibrosis [313] (Figure 6). TGF-β suppresses cytokine and chemokine expression by stimulated mononuclear and endothelial cells.…”

Section: The Role Of Tgf-β In Myocardial Infarctionmentioning

confidence: 99%

The immune system and cardiac repair

Frangogiannis

2008

Pharmacological Research

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572

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Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the role of the immune system in cardiac repair is necessary in order to design optimal strategies for cardiac regeneration.

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The role of TGF-β signaling in myocardial infarction and cardiac remodeling

Cited by 855 publications

References 95 publications

Administration of Pigment Epithelium-Derived Factor Inhibits Left Ventricular Remodeling and Improves Cardiac Function in Rats with Acute Myocardial Infarction

Administration of Pigment Epithelium-Derived Factor Inhibits Left Ventricular Remodeling and Improves Cardiac Function in Rats with Acute Myocardial Infarction

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

The immune system and cardiac repair

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