The Study Of ERK1/2 Madiated Vascular Smooth Muscle Cells Proliferation Stimulated By Apelin-13

AIM: To observe the effect of G protein-coupled receptor APJ endogenous ligand apelin-13 on the proliferation of vascular smooth muscle cells (VSMCs),and investigate whether the effect is related to apelin/APJ-pERK1/2-cyclin D1 signal transduction pathway. Methods: VSMCs were prepared from thoracic aortas of male Sprague-Dawley rats by the explant method. The proliferation and cell cycle were measured by MTT assay and Flow Cytometry (FCM),respectively. Expression of cyclin D1,cyclin E and pERK1/2 were determined by Western blot.Results: MTT assay showed that apelin-13 significantly stimulated VSMCs proliferation in a concentration-dependent manner.FCM analysis showed that apelin-13 stimulated cell cycle progression from G0/G1 to S phase. Apelin-13 decreased the proportion of G0/G1 phase but increased S phase.Western blot analysis showed that apelin-13 promoted the expression of cyclin D1 , cyclin E and pERK1/2.The ERK1/2 inhibitor PD98059 decreased the expression of pERKl/2 induced by apelin-13. Similarly,PD98059 significantly diminished the expression of cyclin D1,and inhibited the VSMCs proliferation stimulated by apelin-13 as well.Conclusion: In the present study, we found that apelin-13 stimulated the proliferation of VSMCs through G0/G1 phase into S phase,and the effects maybe involved in apelin/APJ-pERK1/2-cycln D1 signal cascades.