Class II phosphatidylinositol 3-kinase α and β isoforms are required for vascular smooth muscle Rho activation, contraction and blood pressure regulation in mice.

Class II phosphatidylinositol 3-kinases (PI3K), PI3K-C2α and PI3K-C2β, are involved in cellular processes including endocytosis, cilia formation and autophagy. However, the role of PI3K-C2α and PI3K-C2β at the organismal level is not well understood. We found that double knockout (KO) mice with both smooth muscle-specific KO of PI3K-C2α and global PI3K-C2β KO, but not single KO mice of either PI3K-C2α or PI3K-C2β, exhibited reductions in arterial blood pressure and substantial attenuation of contractile responses of isolated aortic rings. In wild-type vascular smooth muscle cells, double knockdown of PI3K-C2α and PI3K-C2β but not single knockdown of either PI3K markedly inhibited contraction with reduced phosphorylation of 20-kDa myosin light chain and MYPT1 and Rho activation, but without inhibition of the intracellular Ca2+ mobilization. These data indicate that PI3K-C2α and PI3K-C2β play the redundant but essential role for vascular smooth muscle contraction and blood pressure regulation mainly through their involvement in Rho activation.

Citation

Shahidul Islam, Kazuaki Yoshioka, Sho Aki, Kazuhiro Ishimaru, Hiroki Yamada, Noriko Takuwa, Yoh Takuwa. Class II phosphatidylinositol 3-kinase α and β isoforms are required for vascular smooth muscle Rho activation, contraction and blood pressure regulation in mice. The journal of physiological sciences : JPS. 2020 Mar 19;70(1):18

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PMID: 32192434

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