Complex regulation and function of the inflammatory smooth muscle cell phenotype in atherosclerosis.
Vascular smooth muscle cell (SMC) phenotypic modulation plays a key role in atherosclerosis and is classically defined as a switch from a 'contractile' phenotype to a 'synthetic' phenotype, whereby genes that define the contractile SMC phenotype are suppressed and proliferation and/or migratory mechanisms are induced. There is also evidence that SMCs may take on a 'proinflammatory' phenotype, whereby SMCs secrete cytokines and express cell adhesion molecules, e.g. IL-8, IL-6, and VCAM-1, respectively, which may functionally regulate monocyte and macrophage adhesion and other processes during atherosclerosis. Factors that drive the inflammatory phenotype are not limited to cytokines but also include hemodynamic forces imposed on the blood vessel wall and intimate interaction of endothelial cells with SMCs, as well as changes in matrix composition in the vessel wall. However, it is critical to recognize that our understanding of the complex interaction of these multiple signal inputs has only recently begun to shed light on mechanisms that regulate the inflammatory SMC phenotype, primarily through models that attempt to recreate this environment ex vivo. The goal of this review is to summarize our current knowledge in this area and identify some of the key unresolved challenges and questions requiring further study.
Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, La., USA.
Anthony Wayne
AW
Orr
Nicole E
NE
Hastings
Brett R
BR
Blackman
Brian R
BR
Wamhoff
D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006439:Hemodynamics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D013314:Stress, Mechanical; D014158:Transcription, Genetic
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D018836:Inflammation Mediators