Possible pathophysiological importance of C-terminal tyrosine phosphorylation of CaV1.2 in vessel remodeling

Le résumé fourni par la source

Voltage-dependent CaV1.2 L-type calcium channels play a critical role in the regulation blood pressure. Besides, CaV1.2 is implicated to play a pivotal role in chronic vessel remodeling such as atherosclerosis because several clinical trials indicate that CaV1.2 inhibitors delay the progression of atherosclerosis. However, how CaV1.2 participates in atherogenesis still remains obscure. Vascular smooth muscle cells (VSMC) are critically involved in atherogenesis. Medial VSMCs migrate and proliferate into the intima and form a part of plaque upon endothelial injury. Recently, we have identified that two tyrosine residues in the C-terminus (Tyr1709 and Tyr1758) of VSMC CaV1.2 are phosphorylated by Src-family kinases in response to PDGF. In vitro studies demonstrated that PDGF enhances CaV1.2 channel activity through this phosphorylation, thereby induceing VSMC migration. Thus, CaV1.2 may contribute to vessel remodeling in atherosclerosis. In order to verify this hypothesis, we established a knock-in mice line harboring a mutation at one of the tyrosine residues (Y1709F by using the CRISPR/Cas9 system. Although these mice exhibited no obvious developmental defects, we are now analyzing the effect of carotid artery ligation, a model of intimal thickening in these mice.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.