Macrophage Activation Is Responsible for Loss of Anticontractile Function in Inflamed Perivascular Fat
Macrophage Activation Is Responsible for Loss of Anticontractile Function in Inflamed Perivascular Fat
复制标题
DOI：
10.1161/atvbaha.110.221705
复制
发表时间：
2011-04-01
影响因子：
8.7
通讯作者：
Heagerty, Anthony M.
中科院分区：
文献类型：
--
作者：
Withers, Sarah B.;Agabiti-Rosei, Claudia;Heagerty, Anthony M.
本研究的目的是确定是否巨噬细胞分散在整个血管周围的脂肪是至关重要的抗收缩功能的损失时，健康的脂肪组织变得发炎，并获得有关的机制的理解。使用2种生理炎症刺激物：醛固酮和缺氧，在有和没有血管周围脂肪的情况下进行了10型动物。两种炎症损伤引起血管周围脂肪抗收缩能力的类似丧失和巨噬细胞活化增加。醛固酮受体拮抗剂和自由基清除剂能够恢复这种能力，减少巨噬细胞活化。然而，在小鼠缺乏的巨噬细胞CD 11b-白喉毒素受体（CD 11b-DTR），有没有增加收缩性的动脉醛固酮孵育或hypoxia. Conclusion的存在和激活的巨噬细胞在脂肪组织中是关键的调制器的血管周围脂肪诱导后的动脉收缩性的增加。尽管有多种因素可能参与导致肥胖的血管后果，依普利酮改善醛固酮和缺氧的炎症作用的能力可能具有潜在的治疗意义。（Arterioscler Thromb Vasc Biol.2011;31：908-913.）
Objective-The aim of this study was to determine whether macrophages dispersed throughout perivascular fat are crucial to the loss of anticontractile function when healthy adipose tissue becomes inflamed and to gain an understanding of the mechanisms involved.Methods and Results-Pharmacological studies on in vitro small arterial segments from a mouse model of inducible macrophage ablation and on wild-type animals were carried out with and without perivascular fat using 2 physiological stimuli of inflammation: aldosterone and hypoxia. Both inflammatory insults caused a similar loss of anticontractile capacity of perivascular fat and increased macrophage activation. Aldosterone receptor antagonism and free radical scavengers were able to restore this capacity and reduce macrophage activation. However, in a mouse deficient of macrophages CD11b-diptheria toxin receptor (CD11b-DTR), there was no increase in contractility of arteries following aldosterone incubation or hypoxia.Conclusion-The presence and activation of macrophages in adipose tissue is the key modulator of the increase in contractility in arteries with perivascular fat following induction of inflammation. Despite multiple factors that may be involved in bringing about the vascular consequences of obesity, the ability of eplerenone to ameliorate the inflammatory effects of both aldosterone and hypoxia may be of potential therapeutic interest. (Arterioscler Thromb Vasc Biol. 2011;31:908-913.)