Platelet-derived growth factor involvement in myocardial remodeling following infarction

Abstract

Aims Cardiac remodeling occurs in the infarcted heart (MI). The underlying regulatory mechanisms are under investigation. Platelet-derived growth factor (PDGF) is a family of growth factors that stimulates cell growth, differentiation and migration. Herein, we sought to determine whether PDGF is involved in cardiac repair/remodeling following MI. Methods and Results The temporal and spatial expression of PDGF isoforms (A, B, C and D) and PDGF receptor (PDGFR)-α and β as well as cell types expressing PDGF were examined in the infarcted rat heart. Sham-operated rats served as controls. We found that the normal myocardium expressed all PDGF isoforms, and cell types expressing PDGF were primarily interstitial cells. Following MI, PDGF-A and D were significantly increased in the infarcted myocardium during 6 weeks of the observation period and cells expressing PDGF-A and D were primarily endothelial cells, macrophages and myofibroblasts (myoFb). PDGF-B and C expression was, however, reduced in the infarcted heart. In the noninfarcted myocardium, PDGF-D expression was increased in the late stage of MI and cells expressing PDGF-D were predominantly fibroblasts. Both PDGFR-α and β were significantly increased in the infarcted myocardium in the early and late stages of MI and in the noninfarcted myocardium in the late stage of MI. Conclusions Enhanced PDGF-A, PDGF-D and PDGFR are coincident with angiogenesis, inflammatory and fibrogenic responses in the infarcted myocardium, suggesting their regulation on cardiac repair. Elevated PDGF-D in the noninfarcted myocardium suggests its involvement in the development of interstitial fibrosis that appears in the late stage of MI.

The Role of Platelet-Derived Growth Factor-B/Platelet-Derived Growth Factor Receptor-β Signaling in Chronic Atrial Fibrillation

“…The cardiac-restricted overexpression of either PDGF-C or PDGF-D caused cardiac fibrosis and dilated cardiomyopathy in mice [12,13]. PDGF also plays an important role in cardiac fibrosis after myocardial infarction [14]. Recently, some researches indicated that PDGF may represent a novel mediator of AF.…”

“…Cardiac-restricted overexpression of PDGF-C/D caused cardiac fibrosis and dilated cardiomyopathy in mice [12,13]. PDGF-A/D and PDGF receptor-α/β (PDGFR-α/β) increased in the infarcted heart, which contributed to cardiac fibrosis after myocardial infarction [14]. Cardiac mast cells caused atrial fibrosis, which enhanced AF susceptibility through PDGF-A signaling in pressure-overloaded mouse hearts [15].…”

Getting to the Heart of the Matter

“…84,85 After myocardial infarction, PDGF-A and D are significantly increased in endothelial cells, macrophages, and myofibroblasts. 86 Enhanced PDGF-A, PDGF-D, and PDGF receptors are coincident with angiogenesis and inflammatory and fibrogenic responses in the infarcted myocardium, suggesting their regulation on cardiac repair. 86 Transgenic mice overexpressing the active core domain of PDGF-D in the heart displayed enhanced proliferation of both cardiac interstitial fibroblasts and arterial vascular smooth muscle cells resulting in cardiac fibrosis followed by dilated cardiomyopathy and, subsequently, cardiac failure.…”

“…86 Enhanced PDGF-A, PDGF-D, and PDGF receptors are coincident with angiogenesis and inflammatory and fibrogenic responses in the infarcted myocardium, suggesting their regulation on cardiac repair. 86 Transgenic mice overexpressing the active core domain of PDGF-D in the heart displayed enhanced proliferation of both cardiac interstitial fibroblasts and arterial vascular smooth muscle cells resulting in cardiac fibrosis followed by dilated cardiomyopathy and, subsequently, cardiac failure. 87 In vitro, PDGF-D significantly enhanced TGF-β1 synthesis, which was eliminated by TGF-β blockade with small interfering RNA; moreover, the stimulatory role of PDGF-D on fibroblast proliferation and collagen synthesis was abolished by TGF-β blockade.…”

Cardiac Repair Using Stem Cells Conditioned Media Based Therapy in a Rodent Model of Myocardial Infarction and Heart Failure

“…PDGF has also been identified as a significant contributor to angiogenesis and cardiac remodeling following MI [56][57][58] . Notably, both VEGF and PDGF have demonstrated some adverse effects, particularly when given in high intravenous doses.…”