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首页> 外文期刊>Journal of vascular research >Matrix Metalloproteinase 2 as a Potential Mediator of Vascular Smooth Muscle Cell Migration and Chronic Vascular Remodeling in Hypertension
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Matrix Metalloproteinase 2 as a Potential Mediator of Vascular Smooth Muscle Cell Migration and Chronic Vascular Remodeling in Hypertension

机译:基质金属蛋白酶2作为高血压血管平滑肌细胞迁移和慢性血管重塑的潜在介质

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摘要

For vascular remodeling in hypertension, it is essential that vascular smooth muscle cells (VSMCs) reshape in order to proliferate and migrate. The extracellular matrix (ECM) needs to be degraded to favor VSMC migration. Many proteases, including matrix metalloproteinases (MMPs), contribute to ECM proteolysis and VSMC migration. Bioactive peptides, hemodynamic forces and reactive oxygen-nitrogen species regulate MMP-2 expression and activity. Increased MMP-2 activity contributes to hypertension-induced maladaptive arterial changes and sustained hypertension. New ECM is synthesized to supply VSMCs with bioactive mediators, which stimulate hypertrophy. MMP-2 stimulates the interaction of VSMCs with newly formed ECM, which triggers intracellular signaling via integrins to induce a phenotypic switch and persistent migration. VSMCs switch from a contractile to a synthetic phenotype in order to migrate and contribute to vascular remodeling in hypertension. MMPs also disrupt growth factors bound to ECM, thus contributing to their capacity to regulate VSMC migration. This review sheds light on the proteolytic effects of MMP-2 on ECM and non-ECM substrates in the vasculature and how these effects contribute to VSMC migration in hypertension. The inhibition of MMP activity as a therapeutic target may make it possible to reduce arterial maladaptation caused by hypertension and prevent the resulting fatal cardiovascular events. (C) 2016 S. Karger AG, Basel
机译:对于高血压中的血管重塑,血管平滑肌细胞(VSMC)的重塑是至关重要的,以使其增殖和迁移。细胞外基质(ECM)需要降解以促进VSMC迁移。许多蛋白酶,包括基质金属蛋白酶(MMP),都有助于ECM蛋白水解和VSMC迁移。生物活性肽,血液动力和活性氧氮调节MMP-2的表达和活性。 MMP-2活性增加导致高血压引起的适应不良的动脉变化和持续性高血压。合成了新的ECM,为VSMC提供生物活性介质,从而刺激肥大。 MMP-2刺激VSMC与新形成的ECM相互作用,后者通过整联蛋白触发细胞内信号传导,以诱导表型转换和持续迁移。 VSMC从可收缩表型转变为合成表型,以迁移并有助于高血压中的血管重塑。 MMP还会破坏与ECM相关的生长因子,从而有助于其调节VSMC迁移的能力。这篇综述揭示了MMP-2对脉管系统中ECM和非ECM底物的蛋白水解作用,以及这些作用如何促进高血压中的VSMC迁移。作为治疗靶的MMP活性的抑制可以减轻由高血压引起的动脉适应不良并预防致命的心血管事件。 (C)2016 S.Karger AG,巴塞尔

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