Published online before print February 14, 2008, doi: 10.1161/ATVBAHA.107.159327
© 2008 American Heart Association, Inc.
Brief Review |
Role of Smooth Muscle Cells in the Initiation and Early Progression of Atherosclerosis
From the Cardiovascular Division/Department of Medicine, the Cardiovascular Research Center, and Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville.
Correspondence to Coleen A. McNamara, University of Virginia Health Sciences Center, Cardiovascular Division, PO Box 801394, Charlottesville, VA 22908. E-mail cam8c{at}virginia.edu
The initiation of atherosclerosis results from complex interactions of circulating factors and various cell types in the vessel wall, including endothelial cells, lymphocytes, monocytes, and smooth muscle cells (SMCs). Recent reviews highlight the role of activated endothelium and inflammatory cell recruitment in the initiation of and progression of early atherosclerosis. Yet, human autopsy studies, in vitro mechanistic studies, and in vivo correlative data suggest an important role for SMCs in the initiation of atherosclerosis. SMCs are the major producers of extracellular matrix within the vessel wall and in response to atherogenic stimuli can modify the type of matrix proteins produced. In turn, the type of matrix present can affect the lipid content of the developing plaque and the proliferative index of the cells that are adherent to it. SMCs are also capable of functions typically attributed to other cell types. Like macrophages, SMCs can express a variety of receptors for lipid uptake and can form foam-like cells, thereby participating in the early accumulation of plaque lipid. Like endothelial cells, SMCs can also express a variety of adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 to which monocytes and lymphocytes can adhere and migrate into the vessel wall. In addition, through these adhesion molecules, SMCs can also stabilize these cells against apoptosis, thus contributing to the early cellularity of the lesion. Like many cells within the developing plaque, SMCs also produce many cytokines such as PDGF, transforming growth factor-β, IFN
, and MCP-1, all of which contribute to the initiation and propagation of the inflammatory response to lipid. Recent advances in SMC-specific gene modulation have enhanced our ability to determine the role of SMCs in early atherogenesis.
Smooth muscle cells (SMCs) play a key role in fibrous cap formation and plaque stability in advanced atherosclerosis; however, less is known about the role of SMCs in the initiation and progression of atherosclerosis. This review summarizes the present data implicating SMCs in the development of early atherogenesis.
Key Words: atherosclerosis • smooth muscle cells • intimal thickening
This article has been cited by other articles:
 |
|
 |
|
  S I Chisalita, G S Johansson, E Liefvendahl, K Back, and H J Arnqvist Human aortic smooth muscle cells are insulin resistant at the receptor level but sensitive to IGF1 and IGF2 J. Mol. Endocrinol., December 1, 2009; 43(6): 231 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-L. Hsieh, W.-H. Tung, C.-Y. Wu, H.-H. Wang, C.-C. Lin, T.-S. Wang, and C.-M. Yang Thrombin Induces EGF Receptor Expression and Cell Proliferation via a PKC({delta})/c-Src-Dependent Pathway in Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1594 - 1601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Kim, E.-K. Yoo, J.-Y. Kim, Y.-K. Choi, H.-J. Lee, J.-K. Kim, N. H. Jeoung, K.-U. Lee, I.-S. Park, B.-H. Min, et al. Protective Role of Clusterin/Apolipoprotein J Against Neointimal Hyperplasia via Antiproliferative Effect on Vascular Smooth Muscle Cells and Cytoprotective Effect on Endothelial Cells Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1558 - 1564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Lyle, N. N. Deshpande, Y. Taniyama, B. Seidel-Rogol, L. Pounkova, P. Du, C. Papaharalambus, B. Lassegue, and K. K. Griendling Poldip2, a Novel Regulator of Nox4 and Cytoskeletal Integrity in Vascular Smooth Muscle Cells Circ. Res., July 31, 2009; 105(3): 249 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Eichhorn, G. Muller, A. Leuner, T. Sawamura, U. Ravens, and H. Morawietz Impaired vascular function in small resistance arteries of LOX-1 overexpressing mice on high-fat diet Cardiovasc Res, June 1, 2009; 82(3): 493 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
N. Leitinger "Obese" Smooth Muscle Cells Fail to Assemble Collagen Fibrils Circ. Res., April 10, 2009; 104(7): 826 - 828. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Nakagawa, Y. Morikawa, Y. Mizuno, E. Harada, T. Ito, K. Matsui, Y. Saito, and H. Yasue Coronary Spasm Preferentially Occurs at Branch Points: An Angiographic Comparison With Atherosclerotic Plaque Circ Cardiovasc Interv, April 1, 2009; 2(2): 97 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Reddy, S. Sahar, L. M. Villeneuve, L. Lanting, and R. Natarajan Role of Src Tyrosine Kinase in the Atherogenic Effects of the 12/15-Lipoxygenase Pathway in Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 387 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Chatterjee, L. L. Stoll, G. M. Denning, A. Harrelson, A. L. Blomkalns, G. Idelman, F. G. Rothenberg, B. Neltner, S. A. Romig-Martin, E. W. Dickson, et al. Proinflammatory Phenotype of Perivascular Adipocytes: Influence of High-Fat Feeding Circ. Res., February 27, 2009; 104(4): 541 - 549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Liu, Y. Cheng, S. Zhang, Y. Lin, J. Yang, and C. Zhang A Necessary Role of miR-221 and miR-222 in Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia Circ. Res., February 27, 2009; 104(4): 476 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, X. Zhao, H. Jin, H. Wei, W. Li, D. Bu, X. Tang, Y. Ren, C. Tang, and J. Du Role of Hydrogen Sulfide in the Development of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice Arterioscler Thromb Vasc Biol, February 1, 2009; 29(2): 173 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Orr, M. Y. Lee, J. A. Lemmon, A. Yurdagul Jr, M. F. Gomez, P. D. Schoppee Bortz, and B. R. Wamhoff Molecular Mechanisms of Collagen Isotype-Specific Modulation of Smooth Muscle Cell Phenotype Arterioscler Thromb Vasc Biol, February 1, 2009; 29(2): 225 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Lamon and D. P. Hajjar Inflammation at the Molecular Interface of Atherogenesis: An Anthropological Journey Am. J. Pathol., November 1, 2008; 173(5): 1253 - 1264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, M. A. Reddy, F. Miao, N. Shanmugam, J.-K. Yee, D. Hawkins, B. Ren, and R. Natarajan Role of the Histone H3 Lysine 4 Methyltransferase, SET7/9, in the Regulation of NF-{kappa}B-dependent Inflammatory Genes: RELEVANCE TO DIABETES AND INFLAMMATION J. Biol. Chem., September 26, 2008; 283(39): 26771 - 26781. [Abstract] [Full Text] [PDF]
|
|