Tang Paul C Y, Qin Lingfeng, Zielonka Jacek, Zhou Jing, Matte-Martone Catherine, Bergaya Sonia, van Rooijen Nico, Shlomchik Warren D, Min Wang, Sessa William C, Pober Jordan S, Tellides George
Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT 06510, USA.
J Exp Med. 2008 Dec 22;205(13):3159-71. doi: 10.1084/jem.20081298. Epub 2008 Dec 8.
Vascular remodeling normalizes abnormal hemodynamic stresses through structural changes affecting vessel size and wall thickness. We investigated the role of inflammation in flow-mediated vascular remodeling using a murine model of partial outflow reduction without flow cessation or neointima formation. Common carotid arteries decreased in size after ipsilateral external carotid artery ligation in wild-type mice, but not in myeloid differentiation protein-88 (MyD88)-deficient mice. Inward remodeling was associated with MyD88-dependent and superoxide-initiated cytokine and chemokine production, as well as transient adventitial macrophage accumulation and activation. Macrophage depletion prevented flow-mediated inward vascular remodeling. Expression of MyD88 by intrinsic vascular cells was necessary for cytokine and chemokine production and changes in vessel size, whereas MyD88 expression by bone marrow-derived cells was obligatory for changes in vessel size. We conclude that there are at least two distinct roles for MyD88 in flow-mediated inward remodeling of conduit arteries. Our findings suggest that inflammation is necessary for vascular adaptation to changes in hemodynamic forces.
血管重塑通过影响血管大小和壁厚度的结构变化使异常血流动力学应力正常化。我们使用部分流出减少但无血流停止或新内膜形成的小鼠模型，研究了炎症在血流介导的血管重塑中的作用。野生型小鼠同侧颈外动脉结扎后，颈总动脉尺寸减小，但髓样分化蛋白88（MyD88）缺陷小鼠则不然。内向重塑与MyD88依赖性和超氧化物引发的细胞因子及趋化因子产生，以及短暂的外膜巨噬细胞积聚和激活有关。巨噬细胞耗竭可防止血流介导的内向血管重塑。内在血管细胞表达MyD88对于细胞因子和趋化因子产生及血管大小变化是必需的，而骨髓源性细胞表达MyD88对于血管大小变化是必不可少的。我们得出结论，MyD88在传导动脉血流介导的内向重塑中至少有两个不同作用。我们的研究结果表明，炎症对于血管适应血流动力学力的变化是必要的。
