Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling |
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| Authors: | Fu Gao Pierre Chambon George Tellides Wei Kong Xiaoming Zhang Wei Li |
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| Institution: | 1. Department of Vascular Surgery, Peking University People’s Hospital, Beijing, People’s Republic of China;2. Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS UMR7104; INSERM U596; ULP, Collége de France) and Institut Clinique de la Souris, ILLKIRCH, Strasbourg, France;3. Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT, USA;4. Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing, People’s Republic of China |
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| Abstract: | Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2f/f) and their corresponding wild-type background mice (MyhCre.Tgfbr2WT/WT) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process. |
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| Keywords: | TGF-β transforming growth factor-β MMP matrix metalloproteinase SMC smooth muscle cell Tgfbr2 TGF-β type II receptor MCP1 monocyte chemoattractant protein 1 MIP1α macrophage inflammatory protein 1α SM smooth muscle ECM extracellular matrix LCA left carotid artery |
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