OBJECTIVE: Vascular smooth muscle cells (VSMCs) may regulate monocyte functions within atherosclerotic lesions. We investigated the impact of VSMC/monocyte interactions on monocyte apoptosis and scavenger receptor CD36 expression, key events related to monocyte survival and differentiation. METHODS AND RESULTS: Serum deprivation significantly increased THP-1 and human peripheral blood monocyte apoptosis. However, this was significantly reversed by physical binding to human VSMCs (HVSMCs). On binding to HVSMCs, antiapoptotic kinase Akt and its downstream targets were phosphorylated, and Bcl-2 expression was enhanced. Binding-mediated suppression of apoptosis and Akt phosphorylation were attenuated by a phosphoinositide 3-kinase inhibitor and also by an antibody to vascular cell adhesion molecule-1. CD36 expression was also significantly increased in THP-1 cells and in human peripheral blood monocytes after binding to HVSMCs, and this was mediated by both direct contact and soluble factors. Extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase phosphorylation was increased in THP-1 cells after HVSMC coculture. Furthermore, an ERK1/2 inhibitor blocked monocyte CD36 upregulation. Contact-dependent CD36 induction and ERK1/2 phosphorylation in monocytes were inhibited by blocking vascular cell adhesion molecule-1 on HVSMC, whereas soluble factor-induced CD36 expression was attenuated by a monocyte chemoattractant protein-1 neutralizing antibody. CONCLUSIONS: These data provide evidence of novel VSMC-dependent local regulation mechanisms for monocyte survival and differentiation in atherosclerosis.
OBJECTIVE: Vascular smooth muscle cells (VSMCs) may regulate monocyte functions within atherosclerotic lesions. We investigated the impact of VSMC/monocyte interactions on monocyte apoptosis and scavenger receptor CD36 expression, key events related to monocyte survival and differentiation. METHODS AND RESULTS: Serum deprivation significantly increased THP-1 and human peripheral blood monocyte apoptosis. However, this was significantly reversed by physical binding to human VSMCs (HVSMCs). On binding to HVSMCs, antiapoptotic kinase Akt and its downstream targets were phosphorylated, and Bcl-2 expression was enhanced. Binding-mediated suppression of apoptosis and Akt phosphorylation were attenuated by a phosphoinositide 3-kinase inhibitor and also by an antibody to vascular cell adhesion molecule-1. CD36 expression was also significantly increased in THP-1 cells and in human peripheral blood monocytes after binding to HVSMCs, and this was mediated by both direct contact and soluble factors. Extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase phosphorylation was increased in THP-1 cells after HVSMC coculture. Furthermore, an ERK1/2 inhibitor blocked monocyte CD36 upregulation. Contact-dependent CD36 induction and ERK1/2 phosphorylation in monocytes were inhibited by blocking vascular cell adhesion molecule-1 on HVSMC, whereas soluble factor-induced CD36 expression was attenuated by a monocyte chemoattractant protein-1 neutralizing antibody. CONCLUSIONS: These data provide evidence of novel VSMC-dependent local regulation mechanisms for monocyte survival and differentiation in atherosclerosis.
Authors: Hossein Bayat; Katrin Schröder; David R Pimentel; Ralf P Brandes; Tony J Verbeuren; Richard A Cohen; Bingbing Jiang Journal: Free Radic Biol Med Date: 2012-03-09 Impact factor: 7.376
Authors: Sara Hägg; Josefin Skogsberg; Jesper Lundström; Peri Noori; Roland Nilsson; Hua Zhong; Shohreh Maleki; Ming-Mei Shang; Björn Brinne; Maria Bradshaw; Vladimir B Bajic; Ann Samnegård; Angela Silveira; Lee M Kaplan; Bruna Gigante; Karin Leander; Ulf de Faire; Stefan Rosfors; Ulf Lockowandt; Jan Liska; Peter Konrad; Rabbe Takolander; Anders Franco-Cereceda; Eric E Schadt; Torbjörn Ivert; Anders Hamsten; Jesper Tegnér; Johan Björkegren Journal: PLoS Genet Date: 2009-12-04 Impact factor: 5.917