Protein kinase C regulates vascular calcification via cytoskeleton reorganization and osteogenic signaling.

Biochemical and biophysical research communications

PubMedID: 25445591

Lee K, Kim H, Jeong D. Protein kinase C regulates vascular calcification via cytoskeleton reorganization and osteogenic signaling. Biochem Biophys Res Commun. 2014;453(4):793-797.
Vascular calcification is an active cell-mediated process that reduces elasticity of blood vessels and increases blood pressure. Until now, the molecular basis of vascular calcification has not been fully understood. We previously reported that microtubule disturbances mediate vascular calcification. Here, we found that protein kinase C (PKC) signaling acted as a novel coordinator between cytoskeletal changes and hyperphosphatemia-induced vascular calcification. Phosphorylation and expression of both PKCa and PKCd decreased during inorganic phosphate (Pi)-induced vascular smooth muscle cell (VSMC) calcification. Knockdown of PKC isoforms by short interfering RNA as well as PKC inactivation by Go6976 or rottlerin treatment revealed that specific inhibition of PKCa and PKCd accelerated Pi-induced calcification both in VSMCs and ex vivo aorta culture through upregulation of osteogenic signaling. Additionally, inhibition of PKCa and PKCd induced disassembly of microtubule and actin, respectively. In summary, our results indicate that cytoskeleton perturbation via PKCa and PKCd inactivation potentiates vascular calcification through osteogenic signal induction.