Shear Stress Modulates Proliferation Of Vascular Cells Via RACK1and Protein Kinase

Vascular remodeling is the essential pathological process ofatherosclerosis which threatening the human health.In vivo, the cardiovascular system is a complex mechanical system,and hemodynamic is one of the most important factors that effect vascularremodeling. Many evidences had revealed that atherosclerosis often occursin the bifurcation and curve of the vessel which suggests that LowSS is animportant trigger for vascular remodeling. However, the molecularmechanism involved in this process is still unclear. In our previousproteomic study, we found receptor for activated C kinase1(RACK1) washighly expressed in LowSS (5dyn/cm2) cultured rat aorta, in comparisonwith normal shear stress (NSS,15dyn/cm2). RACK1is as an importantregulator of protein kinase (protein kinase, PK), but its mechanism in theregulation of vascular remodeling induced by shear stress is still not clear.Using EC/VSMC co-cultured parallel plate flow chamber system, twolevels of shear stress, i.e. LowSS (5dyne/cm2) and NSS (15dyne/cm2),respectively were applied for12h. We use BrdU ELISA to detect theproliferation ability of cells. Western blotting was used to detect theexpressions of RACK1, phospho-Akt, phospho-PKCα/βII andphospho-PKD on the2kinds of residues, i.e. ser916and ser744. To find the effect of RACK1on the proliferation of ECs and VSMCs, RNAinterference (RNAi) was used to inhibit the expression of RACK1in ECsand VSMCs.The results revealed that:(1) Compared with NSS, the proliferation ofECs and VSMCs was significantly increased by LowSS.(2) Theexpression of RACK1, and phosphorylation of Akt, PKCα/βII and PKD onser916residue in ECs and VSMCs were significantly increased by theLowSS application, while phosphorylation of PKD ser744residue was notsignificantly changed.(3) Target RNAi of RACK1significantly decreasedthe proliferation of ECs and VSMCs.(4) Target RNAi of RACK1significantly decreased the phosphorylation of Akt, PKCα/βII and PKDser916residue.The present results suggested that LowSS may increase theexpression of RACK1and then up-regulate the phosphorylation of Akt,PKCα/βII and PKD916in ECs and VSMCs, which subsequently regulatedcell proliferation during vascular remodeling.