Pigment epithelium-derived factor attenuates myocardial fibrosis via inhibiting Endothelial-to-Mesenchymal Transition in rats with acute myocardial infarction.
Endothelial mesenchymal transition (EndMT) plays a critical role in the pathogenesis and progression of interstitial and perivascular fibrosis after acute myocardial infarction (AMI). Pigment epithelium-derived factor (PEDF) is shown to be a new therapeutic target owing to its protective role in cardiovascular disease. In this study, we tested the hypothesis that PEDF is an endogenous inhibitor of EndMT and represented a novel mechanism for its protective effects against overactive cardiac fibrosis after AMI. Masson's trichrome (MTC) staining and picrosirius red staining revealed decreased interstitial and perivascular fibrosis in rats overexpressing PEDF. The protective effect of PEDF against EndMT was confirmed by co-labeling of cells with the myofibroblast and endothelial cell markers. In the endothelial cells of microvessels in the ischemic myocardium, the inhibitory effect of PEDF against nuclear translocation of β-catenin was observed through confocal microscopic imaging. The correlation between antifibrotic effect of PEDF and inactivation of β-catenin was confirmed by co-transfecting cells with lentivirus carrying PEDF or PEDF RNAi and plasmids harboring β-catenin siRNA(r) or constitutive activation of mutant β-catenin. Taken together, these results establish a novel finding that PEDF could inhibit EndMT related cardiac fibrosis after AMI by a mechanism dependent on disruption of β-catenin activation and translocation.
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Hao
H
Zhang
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Hongliang
H
Hui
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Zhimin
Z
Li
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Jiajun
J
Pan
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Xia
X
Jiang
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Tengteng
T
Wei
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Huazhu
H
Cui
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Lei
L
Li
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Xulong
X
Yuan
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Teng
T
Sun
Research Facility Center for Morphology, Xuzhou Medical University, Xuzhou 221004, China.
Zhiwei
Z
Liu
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
Zhongming
Z
Zhang
Research Facility Center for Morphology, Xuzhou Medical University, Xuzhou 221004, China.
Hongyan
H
Dong
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D009202:Cardiomyopathies / Q000209:etiology / Q000517:prevention & control*; D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005136:Eye Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D009206:Myocardium / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015843:Serpins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor