Dalton Cardiovascular Research Center, and Department of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri; and.
Am J Physiol Heart Circ Physiol. 2014 Feb 15;306(4):H485-95. doi: 10.1152/ajpheart.00557.2013. Epub 2013 Dec 13.
Inward remodeling is the most prevalent structural change found in the resistance arteries and arterioles of hypertensive individuals. Separate studies have shown that the inward remodeling process requires transglutaminase activation and the polymerization of actin. Therefore, we hypothesize that inward remodeling induced via endogenous transglutaminase activation requires and depends on actin cytoskeletal structures. To test this hypothesis, isolated and cannulated rat cremaster arterioles were exposed to dithiothreitol (DTT) to activate endogenous transglutaminases. DTT induced concentration-dependent vasoconstriction that was suppressed by coincubation with cystamine or cytochalasin-D to inhibit tranglutaminase activity or actin polymerization, respectively. Prolonged (4 h) exposure to DTT caused arteriolar inward remodeling that was also blocked by the presence of cystamine or cytochalasin-D. DTT inwardly remodeled arterioles had reduced passive diameters, augmented wall thickness-to-lumen ratios and altered elastic characteristics that were reverted upon disruption of the actin cytoskeleton with mycalolide-B. In freshly isolated arterioles, exposure to mycalolide-B caused no changes in their passive diameters or their elastic characteristics. These results suggest that, in arterioles, the early stages of the inward remodeling process induced by prolonged endogenous transglutaminase activation require actin dynamics and depend on changes in actin cytoskeletal structures.
内向重构是高血压个体阻力血管和小动脉中最常见的结构变化。单独的研究表明，内向重构过程需要转谷氨酰胺酶激活和肌动蛋白聚合。因此，我们假设通过内源性转谷氨酰胺酶激活诱导的内向重构需要并依赖于肌动蛋白细胞骨架结构。为了验证这一假设，我们对分离并套管的大鼠提睾肌小动脉进行了二硫苏糖醇（DTT）处理以激活内源性转谷氨酰胺酶。DTT 诱导的浓度依赖性血管收缩可被胱胺或细胞松弛素 D 共同孵育抑制，从而分别抑制转谷氨酰胺酶活性或肌动蛋白聚合。长时间（4 小时）暴露于 DTT 会导致小动脉内向重构，而胱胺或细胞松弛素 D 的存在也会阻止这种重构。DTT 内向重塑的小动脉被动直径减小，壁厚度与管腔比值增加，弹性特性改变，而肌抑肽-B 破坏肌动蛋白细胞骨架后可恢复这些特性。在新分离的小动脉中，肌抑肽-B 暴露不会改变其被动直径或弹性特性。这些结果表明，在小动脉中，长期内源性转谷氨酰胺酶激活诱导的内向重构的早期阶段需要肌动蛋白动力学，并依赖于肌动蛋白细胞骨架结构的变化。
