Objective: To investigate the effects and mechanisms of ghrelin on angiogenesis in vulnerable plaque and myocardial infarction. Methods: The ApoE-/-mice were divided into vulnerable plaque group

vulnerable plaque+myocardial infarction group and ghrelin-intervened group. All ApoE-/-mice were fed with a high-fat diet for 12 weeks to induce atherosclerotic vulnerable plaques. The induced-atherosclerotic vulnerable plaque model was established in vulnerable plaque group. The C57BL/6J mice were fed for 12 weeks on a normal diet and divided into control group and myocardial infarction group. At the 8th week of this study

myocardial infarction group

vulnerable plaque+myocardial infarction group and ghrelin group were subjected to acute myocardial infarction model. After this model

the ghrelin group was administered ghrelin (100 μg/kg

bid) until the end of the 12th week. The left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were detected by echocardiography and the percentage of atherosclerotic plaque area in aortic sinus was observed by Oil red O staining. The microvascular density (MVD) in vulnerable plaque and surrounding area of myocardial infarction were measured by CD31 immunohistochemistry and Masson staining

respectively. The mRNA and protein expression of vascular endothelial growth factor (VEGF)

angiopoietins (Ang) -1/2 and tyrosine-protein kinase receptor (Tie) -2 were respectively examined by real-time PCR and Western blot. Results: ①Compared with myocardial infarction group

the myocardial infarct size in vulnerable plaque+myocardial infarction group [(65.518±4.160) %

P=0.000]was increased

whereas the LVEF [(58.560±11.900) %

P=0.012]and LVFS [(27.182±7.807) %

P=0.013]

the MVD (5.800±0.837

P=0.000) in the peripheral area of myocardial infarction

and the expression of VEGF (1.870±0.122

P=0.001)

Ang-1 (1.830±0.056

P=0.007)

Ang-2 (1.660±0.217

P=0.006) and Tie-2 (1.660±0.115

P=0.020) were decreased

significantly. Additionally

the ghrelin intervention had significantly reduced myocardial infarct size [(39.751±3.039) %

P=0.000]

and improved LVEF [(74.679±6.535) %

P=0.013]

LVFS [(37.507±5.210) %

P=0.020]

the MVD (9.857±1.345

P=0.000) in the peripheral area of myocardial infarction

and the expression of VEGF (3.503±0.384

P=0.004)

Ang-1 (3.277±0.186

P=0.017)

Ang-2 (3.450±0.187

P=0.000) and Tie-2 (3.133±0.139

P=0.009) of the vulnerable plaque+myocardial infarction group.②There were no significant differences in the percentage of aortic sinus plaque area

the MVD in vulnerable plaque

and the expression of VEGF

Ang-1

Ang-2 and Tie-2 among the vulnerable plaque group

the vulnerable plaque+myocardial infarction group and the ghrelin-intervened group. Regrettably

ghrelin had no effect on angiogenesis in vulnerable plaque+myocardial infarction mice. Conclusion: Ghrelin can promote angiogenesis in ischemic myocardium

reduce myocardial infarct size

and stabilize vulnerable plaque by increasing the mRNA and protein expression of VEGF

Ang-1

Ang-2 and Tie-2.Ghrelin had no effect on angiogenesis in vulnerable plaque of vulnerable plaque+myocardial infarction group.