Abstract: Objective To investigate the effects and mechanisms of ghrelin on plaque stability and endothelial funtion in ApoE^-/- mice after myocardial infarction. Methods The ApoE^-/- mice were divided into control group, double model group and ghrelin-treated group. All ApoE^-/- mice were fed with a high-fat diet for 12 weeks to induce atherosclerotic vulnerable plaques. The atherosclerotic vulnerable plaque model was the control group.At the 8th week of this study, the double model group and the ghrelin group were subjected to acute myocardial infarction model(AMI). After modeling of AMI, the ghrelin group was administered with ghrelin (100 μg/kg,bid) until the end of the 12th week. Body weight and blood lipids were detected. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were recorded by echocardiography; NO level was measured by Griess method; the percentage of aortic sinus plaque area was evaluated by HE microscopy. The plaque content of lipid and collagen was observed by Oil Red 0 and Sirius red staining; The distribution of macrophages and smooth muscle cells in plaques were determined by RAM-11 and α-actin immunohistochemical staining and microscopy; And then the vulnerability index was calculated; Myocardial infarct size was measured by Masson staining and microscopy; The vascular endothelial growth factor (VEGF) was detected by quantitative real-time PCR and Western blot. Results Compared with the control group, the level of LVEF and LVFS and NO₂^-/NO₃^- concentration in the double model group were all decreased(P＜0.05), and the expression of VEGF was increased(P＜0.05), significantly. However, the ghrelin group had significantly reduced plasma TG level and also the myocardial infarct size(P＜0.05), LVEF, LVFS, NO₂^-/NO₃^- level, the expression of VEGF, and the plaque content of collagen and smooth muscle cells were all increased(P＜0.05), and reduced the percentage of aortic sinus plaque area, the distribution of lipid and macrophages(P＜0.05), and the vulnerability index as compared with the double model group(P＜0.05). Conclusions 1)Ghrelin may improve the endothelial function and improve heart function in ApoE^-/- mice after myocardial infarction. 2)Ghrelin may stabilize vulnerable plaque and reduce the occurrence of reinfarction.

Key words: ghrelin, vulnerable plaque, myocardial infarction, endothelial function, ApoE^-/- mice