Insulin induces PKC-dependent proliferation of mesenteric vascular smooth muscle cells from hypertensive patients

Background and objectives Proliferation of human vascular smooth muscle cells (VSMCs) induced by hyperinsulinemia is a very common clinical pathology. Extensive research has focused on PKC (Protein kinase C)-MAPK (mitogen-activated protein kinase) intracellular signal transduction and the phenotypic modulation accompanied by reorganization of intracellular F-actins in VSMCs. Methods DNA synthesis, signaling of ERK1/2 MAPKs, and changes in a-smooth muscle (SM) actin and F-actin were studied in hypertensive and normotensive human arterial VSMCs exposed to insulin and PMA with and without the PKC inhibitor, GF109203X. Results Differences among cell types in MAPK signaling, a-SM actin, and F-actin isoforms in VSMCs harvested from the arteries of patients with essential hypertension (EH) and normotension (NT) were identified in response to insulin treatment. Proliferation and activation of MAPK were more pronounced in EH VSMCs than in NEH VSMCs. Insulin exposure decreased expression of a-SM actin and was accompanied by rearrangement of intracellular F-actins in VSMCs, especially in the EH group. These effects were reversed by treatment with the PKC inhibitor. Conclusions Human mesenteric VSMCs of EH and NT patients differed in proliferation, MAPK signaling, and degree of changes in a-SM actin and F-actin isoforms immediately following insulin exposure in vitro.