Nasim Hedayati, Hong Chai, Lyssa N. Ochoa, Peter H. Lin, Alan B Lumsden, Qizhi Yao, Changyi Chen
Baylor College of Medicine, Houston, TX
Objective: Ghrelin, a novel growth hormone-releasing peptide, is implicated to play a role in cardiovascular tissues. However, it is unclear whether ghrelin protects vascular tissue from injury secondary to risk factors such as homocyteine (Hcy). The purpose of this study was to investigate the effect and potential mechanisms of ghrelin on Hcy-induced endothelial dysfunction.
Methods: Porcine coronary artery rings were incubated for 24 hours as control, or with ghrelin (100ng/ml), Hcy (50μM), or ghrelin plus Hcy. Endothelial vasomotor function was evaluated using the myograph tension model. The response to thromboxane A2 analog U466419, bradykinin, and sodium nitroprusside (SNP) was analyzed. Finally, endothelial nitric oxide synthetase (eNOS) expression was determined using real time PCR and superoxide anion production was analyzed by lucigenin-enhanced chemiluminescence.
Results: Maximal contraction with U466419 and endothelium-independent relaxation with SNP were not different among the four groups. However, endothelium-dependent relaxation with bradykinin (10-6M) was significantly reduced by 34% with Hcy as compared to controls (p<0.05). Addition of ghrelin to Hcy had a protective effect, with 61.6% relaxation, similar to controls (64.7%). Hcy significantly reduced eNOS expression, while ghrelin co-treatment effectively restored eNOS expression to control levels. Superoxide anion levels which were increased by 100% with Hcy, returned to control levels with ghrelin co-treatment.
Conclusions: We have demonstrated that ghrelin has a protective effect in the coronary artery by blocking Hcy-induced endothelial dysfunction, improving eNOS expression, and reducing oxidative stress. Ghrelin administration may have beneficial effects in the treatment of atherosclerotic disease in patients with hyperhomocysteinemia.