Comparison Of GSTp And GSTm On Inhibiting Ang â…¡Induced VSMCs Proliferation And Its Mechanism

Vascular smooth muscle cells (VSMCs) are one of the major constituents of blood vessel walls responsible for the maintenance of vessel structures and functions. VSMCs proliferation and migration from media of artery to intima has been considered to be key events in the development of atherosclerosis, hypertension and restenosis. Angiotensin â…¡ is one of the most important factor which can induce VSMCs proliferation. Angiotensin â…¡ up-regulates reactive oxygen species in VSMCs and activates several signaling pathways which will finally induce VSMCs proliferation.The glutathione S-transferases (GST) are a family of phase â…¡ enzymes which play crucial roles in cellular protection against oxidative stress by exhibiting detoxification and radical scavenging activities. GST catalyze the nucleophilic attack of the sulfur atom of glutathione (GSH) on electrophilic groups of substrate molecules. Among the seven isozymes, glutathione S-transferase p (GSTp) is the most prevalent one in mammalian cells,whicn can scavenge reactive oxygen species (ROS) in cells and combine with other molecular. Recent study showed that GSTm, another isoenzyme of GST, played an inhibitive effect on VSMCs proliferation and oxidative stress.Our lab had found that GSTp also inhibited VSMCs proliferation and migration.The present study was to compare the inbitive effect of GSTp and GSTm on VSMCs proliferation, and to investgate the mechanisms in it.Here, we report that GSTp inhibited VSMCs proliferation and arrests the cell cycle at G0/G1phase; the inbitive effect of GSTp was stronger than GSTm; down-regulation of GSTp by RNAi reversed this effect; transfection with GSTp decreased phosphorylation of STATS; Y7F, an enzymatic inactive mutant of GSTp, showed weaker inhibitation on VSMCs proliferation and phosphorylation of STAT3; GSTp, GSTm and Y7F showed little inhibitation on phosphorylation of STAT1and STAT5stiumulated by Angll.Our data suggest that GSTp is a better regulator of VSMCs proliferation than GSTm. This function may connect with its transferase activity to specifically reduce phosphorylation of STAT3. These findings provide a new insight for understanding the role of GSTp in maintaining stability of VSMCs and decreasing the risk of atherosclerosis occurrence.