Effects and mechanisms of ghrelin on plaque neovascularization in rabbits with atherosclerosis / 中华内分泌代谢杂志

ABSTRACT

Objective The aim of our study was to investigate the effects and mechanisms of ghrelin on neovascularization in atherosclerosis plaque. Methods 30 male New Zealand rabbits were randomly divided into normal control group ( CON group) , atherosclerosis model group ( AS group) , and ghrelin treatment group ( ghrelin group) , and each group of 10 rabbits. The AS group and ghrelin group underwent balloon-induced arterial wall injury and then fed with high fat diet, the CON group was fed only on a regular diet. They were all fed for 3 months. Then the ghrelin group was given ghrelin 25μg·kg-1 ·d-1 , the other two groups received the same amount of sterile normal saline only. Four weeks later, body weight and blood lipids were detected. The thickness ratio of the intima to media was measured by HE staining. Degree of intra-plaque angiogenesis was evaluated by CD31+ cells immunohisto-chemistry. The vascular endothelial growth factor ( VEGF ) and vascular endothelial growth factor receptor 2 ( VEGFR2) were detected by quantitative realtime PCR and Western blot. The expressions of matrix metalloproteinase ( MMP)-2 and MMP-9 were detected by immunohistochemistry and Western blot. Results ( 1 ) No significant differences in body weight and blood lipids were found between the AS group and the ghrelin group(P>0. 05), but both items were significantly higher than those of the CON group(P<0. 05). (2)The thickness ratio of the intima to media in the ghrelin treated group was distinctly less than that in the AS group(P<0. 05). (3)Compared with the AS group, the ghrelin group showed significantly decreased microvascular density and the expressions of VEGF and VEGFR2 (P<0. 05). (4)Compared with the AS group, ghrelin dramatically inhibited the plaque contents of MMP-2 and MMP-9 ( P<0. 05 ). Conclusions Ghrelin is able to inhibit the growth of neovascularizationin in the atherosclerotic plaque and the development of plaque. And these beneficial effects derive from downregulation of VEGF, VEGFR2, MMP-2, and MMP-9 at the advanced stage of atherosclerosis in rabbits.