Smooth Muscle Cell Derived Microparticles Acts as Autocrine Activation of Smooth Muscle Cell Proliferation by Mitogen Associated Protein Kinase Upregulation.

Microparticles (MP); also know as microvesicles are extracellular vesicles (0.1 to 1.0 m) released by cells in response to cell activation or apoptosis. The high level of circulating MP is one of the important indicators of altered vascular function. Vascular smooth muscle cell (VSMC) derived MP could mediate proliferation and migration of VSMC leading to vascular inflammation. Proliferation of VSMC is mediated by mitogen associated protein kinase (MAPK) and proliferation cell nuclei antigen (PCNA) signaling pathway whereas migration is mediated by metalloproteinase and cytoskeletal remodeling pathway. In this study, VSMC-MP were isolated from confluent VSMC stimulated with tumor necrosis factor (TNF)-. VSMC-MP were treated to VSMC to investigate the VSMC proliferation marker using assay. In comparison to normal (VSMC-MP untreated group), VSMC-MP treatment results in proliferation of VSMC as revealed by MTT assay. VSMC-MP and TNF- induce proliferation by 34% and 67% respectively. VSMC-MP also induce over expression of PCNA in both immuno-fluorescence and western blot experiment. VSMC-MP and TNF- increase the PCNA expression by 1.86-fold and 1.95-fold respectively. Similarly, VSMC-MP treatment results in over expression of MAPK pathway protein expression in VSMC. As compared to normal, the MAPK protein (pERK1/2, pP38 and pJNK) were increased by 1.41-fold, 1.42-fold and 1.48-fold, respectively in VSMC-MP treated VSMC. Our results provide the evidence of VSMC-MP involvement in proliferation of VSMC. Thus, VSMC-MP could be considered as a potential marker of vascular inflammatory disorder such as atherosclerosis.