This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 24/12/2263    most recent 01.ATV.0000146552.16943.5ev1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cai, Q. Articles by Natarajan, R. Search for Related Content PubMed PubMed Citation Articles by Cai, Q. Articles by Natarajan, R. Related Collections Apoptosis Cell signalling/signal transduction Gene expression Other Vascular biology

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2263.)
© 2004 American Heart Association, Inc.

Vascular Biology

Interaction of Monocytes With Vascular Smooth Muscle Cells Regulates Monocyte Survival and Differentiation Through Distinct Pathways

Qiangjun Cai; Linda Lanting; Rama Natarajan

From the Gonda Goldschmied Diabetes Center, Beckman Research Institute of City of Hope, Duarte, Calif.

Correspondence to Rama Natarajan, PhD, Gonda Goldschmied Diabetes Center, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010. E-mail rnatarajan{at}coh.org

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.

We investigated the impact of vascular smooth muscle cell (VSMC)/monocyte interactions on monocyte functions. We observed that VSMC/monocyte interactions led to antiapoptotic effects and increased scavenger receptor CD36 expression in monocytes through distinct signaling pathways. These data provide evidence for a novel VSMC-dependent local regulation of monocyte survival, retention, and differentiation in atherosclerosis.

Key Words: atherosclerosis • monocytes • vascular smooth muscle cells • apoptosis • CD36

This article has been cited by other articles:

				N. E. Hastings, R. E. Feaver, M. Y. Lee, B. R. Wamhoff, and B. R. Blackman Human IL-8 Regulates Smooth Muscle Cell VCAM-1 Expression in Response to Endothelial Cells Exposed to Atheroprone Flow Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 725 - 731. [Abstract] [Full Text] [PDF]

				M. A. Reddy, L. M. Villeneuve, M. Wang, L. Lanting, and R. Natarajan Role of the Lysine-Specific Demethylase 1 in the Proinflammatory Phenotype of Vascular Smooth Muscle Cells of Diabetic Mice Circ. Res., September 12, 2008; 103(6): 615 - 623. [Abstract] [Full Text] [PDF]

				A. C. Doran, N. Meller, and C. A. McNamara Role of Smooth Muscle Cells in the Initiation and Early Progression of Atherosclerosis Arterioscler Thromb Vasc Biol, May 1, 2008; 28(5): 812 - 819. [Abstract] [Full Text] [PDF]

				H. Bayat, S. Xu, D. Pimentel, R. A. Cohen, and B. Jiang Activation of Thromboxane Receptor Upregulates Interleukin (IL)-1 Induced VCAM-1 Expression Through JNK Signaling Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 127 - 134. [Abstract] [Full Text] [PDF]

				K. Ohwaki, H. Bujo, M. Jiang, H. Yamazaki, W. J. Schneider, and Y. Saito A Secreted Soluble Form of LR11, Specifically Expressed in Intimal Smooth Muscle Cells, Accelerates Formation of Lipid-Laden Macrophages Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 1050 - 1056. [Abstract] [Full Text] [PDF]

				D. Namgaladze and B. Brune Phospholipase A2-Modified Low-Density Lipoprotein Activates the Phosphatidylinositol 3-Kinase-Akt Pathway and Increases Cell Survival in Monocytic Cells Arterioscler Thromb Vasc Biol, November 1, 2006; 26(11): 2510 - 2516. [Abstract] [Full Text] [PDF]

				S.-l. Li, M. A. Reddy, Q. Cai, L. Meng, H. Yuan, L. Lanting, and R. Natarajan Enhanced Proatherogenic Responses in Macrophages and Vascular Smooth Muscle Cells Derived From Diabetic db/db Mice Diabetes, September 1, 2006; 55(9): 2611 - 2619. [Abstract] [Full Text] [PDF]

				A. Boullier, Y. Li, O. Quehenberger, W. Palinski, I. Tabas, J. L. Witztum, and Y. I. Miller Minimally Oxidized LDL Offsets the Apoptotic Effects of Extensively Oxidized LDL and Free Cholesterol in Macrophages Arterioscler Thromb Vasc Biol, May 1, 2006; 26(5): 1169 - 1176. [Abstract] [Full Text] [PDF]