Interaction of monocytes with vascular smooth muscle cells regulates monocyte survival and differentiation through distinct pathways

Qiangjun Cai, Linda Lanting, Rama Natarajan

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2263-2270
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number12
DOIs
StatePublished - Dec 1 2004

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Keywords

  • Apoptosis
  • Atherosclerosis
  • CD36
  • Monocytes
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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