PEDF inhibits VEGF-induced vascular leakage through binding to VEGFR2 in acute myocardial infarction

KIZ OpenIR

	PEDF inhibits VEGF-induced vascular leakage through binding to VEGFR2 in acute myocardial infarction
	Hui, HL; Jiang, B; Zhou, YY; Qiu, F; Lin, YG; Li, HM; Li, D; Luo, M; Miao, HR; Ong, SB; Zhang, YQ
	2024
发表期刊	JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
ISSN	0739-1102
摘要	Pigment epithelium-derived factor (PEDF) could bind to vascular endothelial growth factor receptor 2 (VEGFR2) and inhibit its activation induced by VEGF. But how PEDF affects VEGFR2 pathway is still poorly understood. In this study, we elucidated the precise mechanism underlying the interaction between PEDF and VEGFR2, and subsequently corroborated our findings using a rat AMI model. PEDF prevented endocytosis of VE-cadherin induced by hypoxia, thereby protecting the endothelium integrity. A three-dimensional model of the VEGFR2-PEDF complex was constructed by protein-protein docking method. The results showed that the VEGFR2-PEDF complex was stable during the simulation. Hydrogen bonds, binding energy and binding modes were analyzed during molecular dynamics simulations, which indicated that hydrogen bonds and hydrophobic interactions were important for the recognition of VEGFR2 with PEDF. In addition, the results from exudation of fibrinogen suggested that PEDF inhibits vascular leakage in acute myocardial infarction and confirmed the critical role of key amino acids in the regulation of endothelial cell permeability. This observation is also supported by echocardiography studies showing that the 34mer peptide sustained cardiac function during acute myocardial infarction. Besides, PEDF and 34mer could inhibit the aggregation of myofiber in the heart and promoted the formation of a dense cell layer in cardiomyocytes, which suggested that PEDF and 34mer peptide protect against AMI-induced cardiac dysfunction. These results suggest that PEDF inhibits the phosphorylation of downstream proteins, thereby preventing vascular leakage, which provides a new therapeutic direction for the treatment of acute myocardial infarction.Communicated by Ramaswamy H. Sarma
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14430
专题	昆明动物研究所
推荐引用方式 GB/T 7714	Hui, HL,Jiang, B,Zhou, YY,et al. PEDF inhibits VEGF-induced vascular leakage through binding to VEGFR2 in acute myocardial infarction[J]. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS,2024.
APA	Hui, HL.,Jiang, B.,Zhou, YY.,Qiu, F.,Lin, YG.,...&Zhang, YQ.(2024).PEDF inhibits VEGF-induced vascular leakage through binding to VEGFR2 in acute myocardial infarction.JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS.
MLA	Hui, HL,et al."PEDF inhibits VEGF-induced vascular leakage through binding to VEGFR2 in acute myocardial infarction".JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS (2024).

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2024073114.pdf（2956KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文