| Coronary heart disease (CHD) is an important factor that leads to death. The loss of capillary in CHD results in a decrease in the blood supply of myocardiac tissues. Therefore, it is very important to induce angiogenesis and improve the blood supply of myocardiac tissues of CHD. Angiogenesis is the process that new capillaries from existing vessel are formed by sprouting, migration, proliferation of endothelial cell (EC) and extracellular matrix remodelling during wound healing, inflammation, ischemia and tissue anoxia. Angiogenesis involves five steps: (1) the proteolytic degradation of the basement membrane surrounding endothelial cells in a vessel;(2) migration of endothelial cells into the adjacent stroma;(3) proliferation and link of the endothelial cells;(4) lumen formation;(5) remodelling of the extracellular matrix and recruitment of vascular pericytes and coalescence of tubes into loops completes vessel.Angiogenesis is a complex process. It is regulated by many factors. Basement membrane is a key factor. It is composed of fibrilla, non-fibrillar components and heparan sulfate proteoglycan (HSPGs). HSPGs play a very important role in maintaining the function of basement membrane. Perlecan is a major HSPG, which regulates cell proliferation, adhesion and extracellular matrix assembly. Perlecan can bind to some growth factors such as basic fibroblast growth factor (bFGF), avoiding from degradation, enhancing high affinity binging to its receptor, regulating biological activation. However, the role of perlecan in angiogenesis in ischemic myocardium and the signalling pathway underlying has not been fully clarified.The present study evaluates the effect of perlecan in bFGF induced angiogenesis and signalling pathway in vitro and in vivo. The detailed methods are as follows.1. Wistar rats were randomly divided into 3 groups: myocardial infarction group (MI group), bFGF+MI group and sham group. After acute myocardial infarction, bFGF or the same volume saline was injected in the bordermyocardium between infracted and non- infracted areas in bFGF group and MI group. Hemodynamic parameters, the infarct size and microvessel density were observed respectively on 24h, day 14, day28 after operation;perlecan mRNA expression was detected using real time-PCR;FAK expression and p38MAPK phosphorylation were tested using Western blot. The results showed that in bFGF+MI group, the infarct size was significantly smaller, and microvessel density was increased;± d/?/d/max was improved markedly compared with MI group. Perlecan mRNA expression was increased in the infarct marginal and interior zone;Western blot analysis showed that the expression of FAK and p38MAPK phosphorylation was upregulated in bFGF+MI group compared with MI group. It is concluded that perlecan participates in the cardiac protection induced by bFGF. Pathway is related to up-regulation of FAK and p38MAPK.2. This study investigates the effect of perlecan on VSMCs proliferation and the signaling pathway in vitro. The results showed perlecan enhanced the proliferation of VSMCs stimulated by bFGF and up-regulated FAK expression. The bFGF induced proliferation of VSMCs was abolished by preincubated with perlecan antibody, and FAK expression was inhibited.In conclusion, perlecan participates in bFGF induced angiogenesis and cardiac protection, FAK and p38MAPK were involved in the signalling pathway. |
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