| Vascular remodeling is an essential pathology of many cardiovascular diseases, including hypertension and atherosclerosis. It has been reported that low shear stress (LowSS) is associated with vascular remodeling. However, the mechanobiological mechanism by which LowSS induces vascular remodeling has not been well defined yet.In our previous study, the protein profiles of rat aortas cultured under normal shear stress (NSS, 15 dyn/cm2) and LowSS (5 dyn/cm2) ex vivo were compared. 43 differently expressed proteins between the vessels were revealed by two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) analysis. In the present work, the role of receptor for activated C kinase 1 (RACK1), one of the identified proteins by proteomic analysis, in proliferation of ECs and VSMCs was demonstrated. Using parallel-plate flow chamber system, NSS and LowSS were applied to co-cultued ECs and VSMCs for 12 and 24 h respectively. The protein expression of RACK1 in the ECs and VSMCs was detected by using Western blotting. To investigate the effect of RACK1 on EC and VSMC proliferation, and its possible mechanism, the expression of RACK1 in ECs and VSMCs was suppressed by using RNA interference (RNAi). Then, the proliferation of ECs and VSMCs was detected by BrdU ELISA, and the expressions of RACK1 and phospho-Akt were examined by Western blotting.The results showed that LowSS induced RACK1 expression in co-cultured ECs and VSMCs compared with NSS, and the increase of expression in ECs was earlier than that in VSMCs. RACK1 knockdown by RNAi significantly downregulated the proliferation of both ECs and VSMCs, and also enhanced the phoshporylation of Akt in both ECs and VSMCs.Our results indicated that LowSS induced the expression of RACK1 in co-cultured ECs and VSMCs. RACK1 subsequently regulated vascular cell proliferation, which may be related with signal molecule Akt. RACK1 might be a crucial regulator involved in the LowSS-induced vascular remodeling.
|
PDF Full Text Request