The Roles, Mechanisms Of Ghrelin And Obestatin In Coronary Artery Disease And Its Risk Factor

Objective: To investigate changes of circulating ghrelin and obestatin levels, their roles and mechanisms in coronary artery disease (CAD) and obesity.Methods: Plasma total ghrelin and obestatin levels were measured by RIA in CAD and obesity patients. Effect of obestatin on proliferation and differentiation of 3T3-L1 preadipocytes was investigated. Effects of obestatin on isolated rat hearts was investigated in normal and ischemia/reperfusion Langendorff models. Effect of obestatin on proliferation and expression of cell adhesion molecules of H5V endothelial cells was also investigated.Results: Circulating preprandial ghrelin to obestatin ratio was elevated in human obesity. Obestatin inhibited the proliferation and differentiation of 3T3-L1 preadipocytes. Both absolute and relative obestatin levels were increased in CAD patients. Obestatin could deteriorate cardiac function damage induced by ischemia and reperfusion in the Langendorf model of rat heart through the Rho kinase and PI3-K pathways. Obestatin inhibited the proliferation of endothelial cells through the Rho kinase and PI3-K pathways, and increased adhesion molecules expression.Conclusion: There is imbalance of circulating ghrelin and obestatin levels both in CAD and obesity patients, and obestatin may be a new risk factor of CAD.