Effect Of Apelin-13 On Atherosclerosis And Its Mechanism

Atherosclerosis(AS)is an important pathological basis of cardiovascular diseases such as cerebral infarction and myocardial infarction.Atherosclerotic lesions result from an excessive,inflammatory-fibroproliferative response to damage to the endothelium and smooth muscle of the artery wall.A large number of growth factors,cytokines and vasoregulatory molecules invole in this process.Apelin is the endogenous ligand of putative receptorprotein related to the angiotensin receptor ATI(APJ)and is isolated from bovine stomach extract.Apelin-13 is one of the common subtypes of apelin in human blood and can regulate cardiovascular function.So far,how apelin-13 affects the formation of atherosclerosis,there is no definite conclusion.In this study,the effects of apelin-13 on the formation of atherosclerosis and related molecular mechanisms were explored by CCK,Boyden Chamber,qPCR,cell adhesion assay and Western Blotting to find new targets for the treatment of atherosclerosis and provide new theoretical basis.This study found: endogenous expression of APJ receptors was found in human pulmonary artery endothelial cells(HPAECs)and human pulmonary artery smooth muscle cells(HPASMCs).Apelin-13 had no significant effect on the proliferation and migration of HPASMCs and HPAECs.Apelin-13 promoted the adhesion of human promyelocytic leukemia cells(HL60s).qPCR results showed that apelin-13 promoted the expression of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)in HPAECs.Nuclear factor NF-κB Inhibitor(BAY11-7082)inhibited the expression of VCAM-1 and ICAM-1 induced by apelin-13.The interaction between apelin-13 and Angiotensin II(Ang II)was detected by qPCR.The results showed that Ang II induced the expression of VCAM1 and ICAM1,and this effect was significantly inhibited when apelin-13 was administered along with Ang II.Gi protein inhibitor pertussis toxin(PTX)inhibited the expression of VCAM1 and ICAM1 induced by apelin-13 and Ang II.Conclusion: 1.Smooth muscle cells and endothelial cells express APJ receptor.2.Apelin-13 has no significantly effect on the proliferation and migration of smooth muscle cells and endothelial cells.3.Apelin-13 conjugates Gi protein through APJ receptor and activates nuclear transcription factor NF-κB to promote the expression of VCAM-1 and ICAM-1,thereby promoting the adhesion of monocytes and producing pro-atherosclerosis effect.4.Apelin-13 antagonizes the physiological effects of Ang II.