Growth factors induce monocyte binding to vascular smooth muscle cells: Implications for monocyte retention in atherosclerosis

Qiangjun Cai, Linda Lanting, Rama Natarajan

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Adhesive interactions between monocytes and vascular smooth muscle cells (VSMC) may contribute to subendothelial monocyte-macrophage retention in atherosclerosis. We investigated the effects of angiotensin II (ANG II) and platelet-derived growth factor (PDGF)-BB on VSMC-monocyte interactions. Treatment of human aortic VSMC (HVSMC) with ANG II or PDGF-BB significantly increased binding to human monocytic THP-1 cells and to peripheral blood monocytes. This was inhibited by antibodies to monocyte β1 and β2-integrins. The binding was also attenuated by blocking VSMC arachidonic acid (AA) metabolism by inhibitors of 12/15-lipoxygenase (12/15-LO) or cyclooxygenase-2 (COX-2). Conversely, binding was enhanced by overexpression of 12/15-LO or COX-2. Direct treatment of HVSMC with AA or its metabolites also increased binding. Furthermore, VSMC derived from 12/15-LO knockout mice displayed reduced binding to mouse monocytic cells relative to genetic control mice. Using specific signal transduction inhibitors, we demonstrated the involvement of Src, phosphoinositide 3-kinase, and MAPKs in ANG II- or PDGF-BB-induced binding. Interestingly, after coculture with HVSMC, THP-1 cell surface expression of the scavenger receptor CD36 was increased. These results show for the first time that growth factors may play additional roles in atherosclerosis by increasing monocyte binding to VSMC via AA metabolism and key signaling pathways. This can lead to monocyte subendothelial retention, CD36 expression, and foam cell formation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume287
Issue number3 56-3
DOIs
StatePublished - Sep 2004
Externally publishedYes

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Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Monocytes
Atherosclerosis
Intercellular Signaling Peptides and Proteins
Cells
Arachidonic Acid
Angiotensin II
Lipoxygenase
Cyclooxygenase 2
Metabolism
Scavenger Receptors
Signal transduction
Macrophages
Mitogen-Activated Protein Kinase Kinases
Foam Cells
Metabolites
Phosphatidylinositols
1-Phosphatidylinositol 4-Kinase

Keywords

  • Angiotensin II
  • CD36
  • Cell interaction
  • Platelet-derived growth factor-BB

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Growth factors induce monocyte binding to vascular smooth muscle cells : Implications for monocyte retention in atherosclerosis. / Cai, Qiangjun; Lanting, Linda; Natarajan, Rama.

In: American Journal of Physiology - Cell Physiology, Vol. 287, No. 3 56-3, 09.2004.

Research output: Contribution to journalArticle

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