The role of phospholipase C and phosphatidylinositol 3-kinase in vascular smooth muscle cell migration and proliferation

The Journal of Surgical Research
Bo LiuK Craig Kent

Abstract

Vascular smooth muscle cell (SMC) proliferation and migration both contribute to the formation of intimal hyperplasia. Phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI3-K) are ubiquitous signaling proteins that mediate multiple cellular events. In this study, we investigate the role of PLC and PI3-K in platelet-derived growth factor (PDGF) and extracellular matrix protein (ECM) induced SMC proliferation and migration. Proliferation of human saphenous vein SMC was assessed by (3)H-thymidine incorporation. SMC migration was evaluated using a microchemotaxis chamber. U-73122 was used as a general inhibitor for PLC, and D609 and ET-18-OCH3, respectively, were used to block the isotypes of PLC, phosphatidylcholine- (PC-), and phosphatidylinositol- (PI-) specific PLC. PI3-K activity was inhibited using two selective inhibitors, LY-294002 and wortmannin. PDGF and Type 1 collagen (CN-I) stimulated SMC proliferation, whereas PDGF and four distinct extracellular matrix proteins CN-I, Type 4 collagen (CN-IV), fibronectin (FN), and laminin (LN) stimulated SMC migration. Both isotypes of PLC as well as PI3-K were necessary for PDGF- and CN-I-induced proliferation. Signaling for migration, however, was more specific. Of the variou...Continue Reading

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Citations

Nov 21, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jian ShanAndrew R Marks
Feb 21, 2013·Cardiology in Review·Dimitry A ChistiakovAlexander N Orekhov
Oct 10, 2007·Biochemistry. Biokhimii︠a︡·N V ProkazovaE R Andreeva
Dec 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jane E LaucknerKen Mackie
Oct 2, 2007·The Journal of Nutritional Biochemistry·Rafat A SiddiquiGary P Zaloga
Aug 2, 2005·The Journal of Surgical Research·Ankur Chandra, Niren Angle
Jan 16, 2009·Vascular Medicine·Eser AdiguzelMichelle P Bendeck
Jan 27, 2018·Cardiovascular Research·Kerry WadeySarah George
Mar 17, 2007·Circulation Research·William T Gerthoffer
Feb 4, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·David Xing-Fei DengThomas Quertermous
Jan 5, 2019·Journal of the American Heart Association·Signe Holm NielsenIsabel Goncalves
Feb 15, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Kenji SakakibaraK Craig Kent
Jan 10, 2021·Journal of Cardiovascular Translational Research·Rohit MohindraFinosh G Thankam
Nov 12, 2018·ACS Biomaterials Science & Engineering·Bryan D James, Josephine B Allen

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