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Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia
The focus of this review is to provide an overview of the current state of knowledge of molecular mechanisms/processes that control differentiation of vascular smooth muscle cells (SMC) during normal development and maturation of the vasculature, as well as how these mechanisms/processes are altered in vascular injury or disease. A major challenge in understanding differentiation of the vascular SMC is that this cell can exhibit a wide range of different phenotypes at different stages of development, and even in adult organisms the cell is not terminally differentiated. Indeed, the SMC is capable of major changes in its phenotype in response to changes in local environmental cues including growth factors/inhibitors, mechanical influences, cell-cell and cell-matrix interactions, and various inflammatory mediators. There has been much progress in recent years to identify mechanisms that control expression of the repertoire of genes that are specific or selective for the vascular SMC and required for its differentiated function. One of the most exciting recent discoveries was the identification of the serum response factor (SRF) coactivator gene myocardin that appears to be required for expression of many SMC differentiation marker genes, and for initial differentiation of SMC during development. However, it is critical to recognize that overall control of SMC differentiation/maturation, and regulation of its responses to changing environmental cues, is extremely complex and involves the cooperative interaction of many factors and signaling pathways that are just beginning to be understood. There is also relatively recent evidence that circulating stem cell populations can give rise to smooth muscle-like cells in association with vascular injury and atherosclerotic lesion development, although the exact role and properties of these cells remain to be clearly elucidated. The goal of this review is to summarize the current state of our knowledge in this area and to attempt to identify some of the key unresolved challenges and questions that require further study.
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K. M. Lounsbury Preventing Stenosis by Local Inhibition of KCa3.1: A Finger on the Phenotypic Switch Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1036 - 1038. [Full Text] [PDF]
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D.L. Tharp, B.R. Wamhoff, H. Wulff, G. Raman, A. Cheong, and D.K. Bowles Local Delivery of the KCa3.1 Blocker, TRAM-34, Prevents Acute Angioplasty-Induced Coronary Smooth Muscle Phenotypic Modulation and Limits Stenosis Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1084 - 1089. [Abstract] [Full Text] [PDF]
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V. Haydont, B. L. Riser, J. Aigueperse, and M.-C. Vozenin-Brotons Specific signals involved in the long-term maintenance of radiation-induced fibrogenic differentiation: a role for CCN2 and low concentration of TGF-{beta}1 Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1332 - C1341. [Abstract] [Full Text] [PDF]
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D.-W. Lin, I.-C. Chang, A. Tseng, M.-L. Wu, C.-H. Chen, C. A. Patenaude, M. D. Layne, and S.-F. Yet Transforming Growth Factor {beta} Up-regulates Cysteine-rich Protein 2 in Vascular Smooth Muscle Cells via Activating Transcription Factor 2 J. Biol. Chem., May 30, 2008; 283(22): 15003 - 15014. [Abstract] [Full Text] [PDF]
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R. A. Nemenoff, P. A. Simpson, S. B. Furgeson, N. Kaplan-Albuquerque, J. Crossno, P. J. Garl, J. Cooper, and M. C.M. Weiser-Evans Targeted Deletion of PTEN in Smooth Muscle Cells Results in Vascular Remodeling and Recruitment of Progenitor Cells Through Induction of Stromal Cell-Derived Factor-1{alpha} Circ. Res., May 9, 2008; 102(9): 1036 - 1045. [Abstract] [Full Text] [PDF]
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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]
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S. C. Grifoni, S. E. McKey, and H. A. Drummond Hsc70 regulates cell surface ASIC2 expression and vascular smooth muscle cell migration Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2022 - H2030. [Abstract] [Full Text] [PDF]
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 D. Chen, J. M. Abrahams, L. M. Smith, J. H. McVey, R. I. Lechler, and A. Dorling Regenerative repair after endoluminal injury in mice with specific antagonism of protease activated receptors on CD34+ vascular progenitors Blood, April 15, 2008; 111(8): 4155 - 4164. [Abstract] [Full Text] [PDF]
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 J.-J. Hu, A. Ambrus, T. W. Fossum, M. W. Miller, J. D. Humphrey, and E. Wilson Time Courses of Growth and Remodeling of Porcine Aortic Media During Hypertension: A Quantitative Immunohistochemical Examination J. Histochem. Cytochem., April 1, 2008; 56(4): 359 - 370. [Abstract] [Full Text] [PDF]
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 E. Sanchez-Guerrero, V. C. Midgley, and L. M. Khachigian Angiotensin II induction of PDGF-C expression is mediated by AT1 receptor-dependent Egr-1 transactivation Nucleic Acids Res., April 1, 2008; 36(6): 1941 - 1951. [Abstract] [Full Text] [PDF]
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Y. Tang, S. Urs, and L. Liaw Hairy-Related Transcription Factors Inhibit Notch-Induced Smooth Muscle {alpha}-Actin Expression by Interfering With Notch Intracellular Domain/CBF-1 Complex Interaction With the CBF-1-Binding Site Circ. Res., March 28, 2008; 102(6): 661 - 668. [Abstract] [Full Text] [PDF]
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C. E. Chadjichristos, S. Morel, J.-P. Derouette, E. Sutter, I. Roth, A. C. Brisset, M.-L. Bochaton-Piallat, and B. R. Kwak Targeting Connexin 43 Prevents Platelet-Derived Growth Factor-BB-Induced Phenotypic Change in Porcine Coronary Artery Smooth Muscle Cells Circ. Res., March 28, 2008; 102(6): 653 - 660. [Abstract] [Full Text] [PDF]
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E. VanBavel and E. N.T.P. Bakker A Vascular Bone Collector: Arterial Calcification Requires Tissue-Type Transglutaminase Circ. Res., March 14, 2008; 102(5): 507 - 509. [Full Text] [PDF]
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S. Abraham, N. Kogata, R. Fassler, and R. H. Adams Integrin {beta}1 Subunit Controls Mural Cell Adhesion, Spreading, and Blood Vessel Wall Stability Circ. Res., March 14, 2008; 102(5): 562 - 570. [Abstract] [Full Text] [PDF]
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S. J. House and H. A. Singer CaMKII-{delta} Isoform Regulation of Neointima Formation After Vascular Injury Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 441 - 447. [Abstract] [Full Text] [PDF]
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Y. Diao, S. Guthrie, S.-L. Xia, X. Ouyang, L. Zhang, J. Xue, P. Lee, M. Grant, E. Scott, and M. S. Segal Long-Term Engraftment of Bone Marrow-Derived Cells in the Intimal Hyperplasia Lesion of Autologous Vein Grafts Am. J. Pathol., March 1, 2008; 172(3): 839 - 848. [Abstract] [Full Text] [PDF]
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 T. E. Callis, Z. Deng, J.-F. Chen, and D.-Z. Wang Muscling Through the microRNA World Experimental Biology and Medicine, February 1, 2008; 233(2): 131 - 138. [Abstract] [Full Text] [PDF]
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T. Tanaka, H. Sato, H. Doi, C. A. Yoshida, T. Shimizu, H. Matsui, M. Yamazaki, H. Akiyama, K. Kawai-Kowase, T. Iso, et al. Runx2 Represses Myocardin-Mediated Differentiation and Facilitates Osteogenic Conversion of Vascular Smooth Muscle Cells Mol. Cell. Biol., February 1, 2008; 28(3): 1147 - 1160. [Abstract] [Full Text] [PDF]
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 K. Tanaka, M. Sata, T. Natori, J.-r. Kim-Kaneyama, K. Nose, M. Shibanuma, Y. Hirata, and R. Nagai Circulating progenitor cells contribute to neointimal formation in nonirradiated chimeric mice FASEB J, February 1, 2008; 22(2): 428 - 436. [Abstract] [Full Text] [PDF]
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S. Kennard, H. Liu, and B. Lilly Transforming Growth Factor- (TGF- 1) Down-regulates Notch3 in Fibroblasts to Promote Smooth Muscle Gene Expression J. Biol. Chem., January 18, 2008; 283(3): 1324 - 1333. [Abstract] [Full Text] [PDF]
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Y.-J. Han and P. de Lanerolle Naturally Extended CT {middle dot} AG Repeats Increase H-DNA Structures and Promoter Activity in the Smooth Muscle Myosin Light Chain Kinase Gene Mol. Cell. Biol., January 15, 2008; 28(2): 863 - 872. [Abstract] [Full Text] [PDF]
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A. J. Halayko, T. Tran, and R. Gosens Phenotype and Functional Plasticity of Airway Smooth Muscle: Role of Caveolae and Caveolins Proceedings of the ATS, January 1, 2008; 5(1): 80 - 88. [Abstract] [Full Text] [PDF]
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T. Yoshida MCAT Elements and the TEF-1 Family of Transcription Factors in Muscle Development and Disease Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 8 - 17. [Abstract] [Full Text] [PDF]
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M. Moustafa-Bayoumi, M. A. Alhaj, O. El-Sayed, S. Wisel, M. A. Chotani, Z. A. Abouelnaga, M. D. H. Hassona, K. Rigatto, M. Morris, G. Nuovo, et al. Vascular Hypertrophy and Hypertension Caused by Transgenic Overexpression of Profilin 1 J. Biol. Chem., December 28, 2007; 282(52): 37632 - 37639. [Abstract] [Full Text] [PDF]
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G. Lagna, M. M. Ku, P. H. Nguyen, N. A. Neuman, B. N. Davis, and A. Hata Control of Phenotypic Plasticity of Smooth Muscle Cells by Bone Morphogenetic Protein Signaling through the Myocardin-related Transcription Factors J. Biol. Chem., December 21, 2007; 282(51): 37244 - 37255. [Abstract] [Full Text] [PDF]
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K. A. Martin, B. L. Merenick, M. Ding, K. M. Fetalvero, E. M. Rzucidlo, C. D. Kozul, D. J. Brown, H. Y. Chiu, M. Shyu, B. L. Drapeau, et al. Rapamycin Promotes Vascular Smooth Muscle Cell Differentiation through Insulin Receptor Substrate-1/Phosphatidylinositol 3-Kinase/Akt2 Feedback Signaling J. Biol. Chem., December 7, 2007; 282(49): 36112 - 36120. [Abstract] [Full Text] [PDF]
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