Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling
Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling
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DOI：
10.1016/j.bbrc.2014.10.092
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发表时间：
2014-11-07
影响因子：
3.1
通讯作者：
Li, Wei
中科院分区：
文献类型：
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作者：
Gao, Fu;Chambon, Pierre;Li, Wei
转化生长因子-β (TGF-β) 信号传导与血管重塑的发病机制密切相关，尤其是血流诱导的血管重塑的起始和进展。平滑肌细胞（SMC）是动脉壁中的主要驻留细胞，对于动脉重塑至关重要。然而，TGF-β信号在SMC中对血流诱导的血管重塑的作用仍不清楚。因此，我们研究的目的是通过使用遗传平滑肌特异性（SM特异性）TGF-β II型受体（Tgfbr2）缺失小鼠模型来确定SMC中TGF-β途径对血管重塑的影响。 Tgfbr2 表达缺陷的小鼠 (MyhCre.Tgfbr(f/f)) 及其相应的野生型背景小鼠 (MyhCre.Tgfbr2(WT/WT)) 接受左颈总动脉部分结扎 1、2 或 4 周。然后收获颈动脉，表明 SMC 中 Tgfbr2 的破坏对血管重塑具有显着的抑制作用。 Tgfbr2 破坏小鼠的颈动脉中膜增厚、SMC 增殖、巨噬细胞浸润和基质金属蛋白酶 (MMP) 表达均显着减弱。我们的研究首次证明 SMC 中的 TGF-β 信号传导在血流诱导的血管重塑中发挥着重要作用，而破坏可以阻止这一过程。 (C) 2014 Elsevier Inc. 保留所有权利。
Transforming growth factor-beta (TGF-beta) 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-beta signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-beta pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-beta type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr(f/f)) and their corresponding wild-type background mice (MyhCre.Tgfbr2(WT/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-beta signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process. (C) 2014 Elsevier Inc. All rights reserved.