Transmural pressure induces matrix-degrading activity in porcine arteries ex vivo
Transmural pressure induces matrix-degrading activity in porcine arteries ex vivo
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DOI：
10.1152/ajpheart.1999.277.5.h2002
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发表时间：
1999-11-01
影响因子：
4.8
通讯作者：
Galis, ZS
中科院分区：
文献类型：
--
作者：
Chesler, NC;Ku, DN;Galis, ZS
细胞外基质成分必须降解和再合成，以发生血管重塑。我们假设，血流动力学环境调节活性的基质金属蛋白酶（MMPs），在体内基质降解的主要代理商，在血管重塑过程中的跨壁压和剪切力的变化。在离体系统中再现了病理性血流动力学条件，在该系统中，我们将猪颈动脉维持24和48 h。MMP-2和MMP-9的总水平提取的组织匀浆，并通过SDS-PAGE酶谱分析刺激跨壁压和剪切应力的变化不受影响。降解的两个特定的明胶酶底物，明胶和弹性蛋白，随着压力的增加而增加，但降解不受剪切应力的变化，在组织标本分析使用原位酶谱（明胶）和内源性弹性蛋白降解（弹性蛋白）的荧光测量。我们的研究结果表明，跨壁压激活MMP家族的至少两个成员，这些酶的活性伴随着基质成分的降解，可能与高血压血管重塑有关。
Extracellular matrix components must be degraded and resynthesized for vascular remodeling to occur. We hypothesized that the hemodynamic environment regulates activity of matrix metalloproteinases (MMPs), the primary agents for in vivo matrix degradation, during vascular remodeling in response to changes in transmural pressure and shear stress. Pathological hemodynamic conditions were reproduced in an ex vivo system in which we maintained porcine carotid arteries for 24 and 48 h. Total levels of MMP-2 and MMP-9 extracted from tissue homogenates and analyzed by SDS-PAGE zymography were stimulated by transmural pressure and were unaffected by shear stress changes. Degradation of two specific gelatinase substrates, gelatin and elastin, increased with increasing pressure, but the degradation was not affected by shear stress changes in tissue specimens analyzed using in situ zymography (gelatin) and fluorescent measurement of endogenous elastin degradation (elastin). Our results suggest that transmural pressure activates at least two members of the MMP family and that activity of these enzymes is accompanied by degradation of matrix components, effects that may be implicated in hypertensive vascular remodeling.