Collagen inhibitory peptide R1R2 mediates vascular remodeling by decreasing inflammation and smooth muscle cell activation.
Collagen inhibitory peptide R1R2 mediates vascular remodeling by decreasing inflammation and smooth muscle cell activation.
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DOI：
10.1371/journal.pone.0117356
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chiang HY
中科院分区：
文献类型：
--
作者：
Lee TH;Sottile J;Chiang HY
细胞外基质（ECM）是血管壁的主要成分。除了提供结构支架外，ECM 还控制生理和病理环境中的许多细胞功能。血管重塑发生在损伤后，其特征是内皮细胞活化、炎症细胞浸润、平滑肌细胞 (SMC) 的表型调节以及富含胶原蛋白的 ECM 沉积增加。 R1R2 是一种源自细菌粘附素 SFS 的肽，与胶原蛋白具有序列同源性，已知可通过抑制纤连蛋白与胶原蛋白的结合来抑制体外 I 型胶原蛋白沉积。然而，R1R2 在血管重塑过程中的抑制作用尚未被探索。我们在血流停止诱导的血管重塑小鼠模型中使用 Pluronic 凝胶将 R1R2 外膜周围递送至颈动脉，并评估其对内膜中膜增厚、ECM 沉积、SMC 激活和炎症细胞浸润的影响。形态计量分析表明，与对照组相比，R1R2 减少了内膜中层增厚。 R1R2 治疗还减少了血管壁中 I 型胶原蛋白的沉积，并维持 SMC 的收缩表型。有趣的是，R1R2 显着减少了血管内炎症细胞的浸润约 78%。这种减少伴随着 VCAM-1 和 ICAM-1 表达的减少。我们的体外研究表明，R1R2 减弱 SMC 增殖和迁移，还减少单核细胞粘附和通过内皮细胞的跨内皮迁移。总之，这些数据表明 R1R2 通过减少炎症和调节 SMC 增殖和迁移来减弱血管重塑反应，并表明 R1R2 肽可能具有治疗闭塞性血管疾病的治疗潜力。
The extracellular matrix (ECM) is a major constituent of the vessel wall. In addition to providing a structural scaffold, the ECM controls numerous cellular functions in both physiologic and pathologic settings. Vascular remodeling occurs after injury and is characterized by endothelial cell activation, inflammatory cell infiltration, phenotypic modulation of smooth muscle cells (SMCs), and augmented deposition of collagen-rich ECM. R1R2, a peptide derived from the bacterial adhesin SFS, with sequence homology to collagen, is known to inhibit collagen type I deposition in vitro by inhibiting the binding of fibronectin to collagen. However, the inhibitory effects of R1R2 during vascular remodeling have not been explored. We periadventitially delivered R1R2 to carotid arteries using pluronic gel in a vascular remodeling mouse model induced by blood flow cessation, and evaluated its effects on intima-media thickening, ECM deposition, SMC activation, and inflammatory cell infiltration. Morphometric analysis demonstrated that R1R2 reduced intima-media thickening compared to the control groups. R1R2 treatment also decreased collagen type I deposition in the vessel wall, and maintained SMC in the contractile phenotype. Interestingly, R1R2 dramatically reduced inflammatory cell infiltration into the vessel by ∼78%. This decrease was accompanied by decreased VCAM-1 and ICAM-1 expression. Our in vitro studies revealed that R1R2 attenuated SMC proliferation and migration, and also decreased monocyte adhesion and transendothelial migration through endothelial cells. Together, these data suggest that R1R2 attenuates vascular remodeling responses by decreasing inflammation and by modulating SMC proliferation and migration, and suggest that the R1R2 peptide may have therapeutic potential in treating occlusive vascular diseases.
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DOI：
10.1161/01.atv.0000139010.71779.f3
发表时间：
2004-09-01
影响因子：
8.7
作者：
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作者：
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DOI：
10.1016/j.bbrc.2007.02.121
发表时间：
2007-04-27
影响因子：
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作者：
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