Cytosolic Phospholipase A2 Alpha is Required for Human Smooth Muscle Cell Proliferation and Not Migration to Platelet Derived Growth Factor BB

Abstract

Platelet derived growth factor BB (PDGF BB) has an important influence on smooth muscle cell migration and proliferation in restenosis and atherosclerosis. Our understanding of different signal transduction pathways involved in the response of smooth muscle cells to PDGF BB is potentially significant for understanding and manipulating these processes. Prior studies have demonstrated a crucial activation of cytosolic phospholipase A2 (cPLA2) in smooth muscle cells to PDGF BB with the production of arachidonic acid and prostaglandin E2. In this study, we first investigated the role of cPLA2α on human aortic smooth muscle cell (HASMC) migration using modified Boyden chamber assay and under agarose migration studies. AACOCF3 (cPLA2 and iPLA2 inhibitor), 1,2,4-trisubstituted pyrrolidine derivative (cPLA2 inhibitor), and Bromoenol lactone (iPLA2 inhibitor) had no effect on HASMC chemotaxis to PDGF-BB in a modified Boyden chamber. These results were confirmed with specific inhibition of cPLA2α using small interfering RNA (siRNA) showing that HASMC migration was not inhibited in modified Boyden chamber or under agarose migration studies. Using the same siRNA to cPLA2 alpha had very significant inhibition to PDGF-BB dependent HASMC proliferation. These data demonstrate there is a distinct role especially for cPLA2α on human aortic HASMC proliferation and not migration to PDGF-BB.