Small artery remodeling depends on tissue-type transglutaminase
Small artery remodeling depends on tissue-type transglutaminase
复制标题
DOI：
10.1161/01.res.0000151333.56089.66
复制
发表时间：
2005-01-07
影响因子：
20.1
通讯作者：
VanBavel, E
中科院分区：
文献类型：
--
作者：
Bakker, ENTP;Buus, CL;VanBavel, E
小动脉的重塑对于长期调节血压和流向特定器官或组织的血流至关重要。血管直径的很大一部分变化可能是通过血管壁成分的非生长相关重组而发生的。该假设经过检验，组织型转谷氨酰胺酶（tTG）是一种交联酶，有助于小动脉的向内重塑。低血流量诱导的大鼠肠系膜动脉的体内向内重塑可通过抑制 tTG 来减弱。通过蛋白质印迹和免疫染色鉴定，大鼠骨骼肌动脉表达 tTG。在体外，内皮素-1 激活这些动脉会导致向内重塑，但 tTG 抑制剂可阻断这一过程。从大鼠和猪获得的小动脉在暴露于外源性转谷氨酰胺酶后均表现出向内重塑，而添加一氧化氮供体可抑制这种重塑。视黄酸诱导tTG表达增强，在器官培养物中保存3天的猪冠状动脉的向内重塑增加。 tTG 的活性取决于压力。抑制 tTG 可逆转重塑，导致血管直径大幅增加。在胶原蛋白凝胶收缩测定中，tTG 确定平滑肌细胞对胶原蛋白的压缩。总的来说，这些数据表明与慢性血管收缩相关的小动脉重塑取决于组织型转谷氨酰胺酶。这种机制可能揭示与阻力动脉向内重塑相关的病理学的新治疗靶点。
Remodeling of small arteries is essential in the long-term regulation of blood pressure and blood flow to specific organs or tissues. A large part of the change in vessel diameter may occur through non-growth-related reorganization of vessel wall components. The hypothesis was tested that tissue-type transglutaminase (tTG), a cross-linking enzyme, contributes to the inward remodeling of small arteries. The in vivo inward remodeling of rat mesenteric arteries, induced by low blood flow, was attenuated by inhibition of tTG. Rat skeletal muscle arteries expressed tTG, as identified by Western blot and immunostaining. In vitro, activation of these arteries with endothelin-1 resulted in inward remodeling, which was blocked by tTG inhibitors. Small arteries obtained from rats and pigs both showed inward remodeling after exposure to exogenous transglutaminase, which was inhibited by addition of a nitric oxide donor. Enhanced expression of tTG, induced by retinoic acid, increased inward remodeling of porcine coronary arteries kept in organ culture for 3 days. The activity of tTG was dependent on pressure. Inhibition of tTG reversed remodeling, causing a substantial increase in vessel diameter. In a collagen gel contraction assay, tTG determined the compaction of collagen by smooth muscle cells. Collectively, these data show that small artery remodeling associated with chronic vasoconstriction depends on tissue-type transglutaminase. This mechanism may reveal a novel therapeutic target for pathologies associated with inward remodeling of the resistance arteries.