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首页> 外文期刊>Vascular pharmacology >Endothelin-1 (1-31): from chymase-dependent synthesis to cardiovascular pathologies.
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Endothelin-1 (1-31): from chymase-dependent synthesis to cardiovascular pathologies.

机译：内皮素-1（1-31）：从糜酶依赖性合成到心血管疾病。

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摘要

The mast cell-derived serine protease chymase is importantly involved not only in degradation, but in synthesis of bioactive peptides as well. Several studies suggest that chymase is the predominant enzyme in the production of angiotensin II (Ang II) from angiotensin-I in interstitial tissues. Interestingly, chymase has also been suggested to mature endothelin-1 (ET-1) from its precursor, big-ET-1 in vitro. The lack of availability of specific chymase inhibitors, beyond the chymotrypsin-like inhibitor chymostatin, currently hampers the investigation of the chymase/ET-1/Ang II paradigm in physiology and cardiovascular diseases. Nonetheless, the recent advent of highly selective chymase inhibitors is shedding new light on the role of this enzymatic pathway in the several inflammatory prone vascular diseases as summarized in the present review. Considering increasing evidence towards significant interactions between Ang II and ET-1 in cardiovascular diseases, the present review will address the role of chymase in the production of those two peptides. Whether chymase-dependent production of ET-1 plays an important role in cardiovascular pathologies will also be discussed.
机译：肥大细胞衍生的丝氨酸蛋白酶糜蛋白酶不仅重要地参与降解，而且还参与生物活性肽的合成。几项研究表明，糜酶是间质组织中由血管紧张素-I产生血管紧张素II（Ang II）的主要酶。有趣的是，还建议糜蛋白酶在体外从其前体big-ET-1中成熟内皮素-1（ET-1）。除了类似于胰凝乳蛋白酶的抑制剂chymostatin之外，缺乏特定的糜酶抑制剂目前阻碍了对糜蛋白酶/ ET-1 / Ang II范式在生理学和心血管疾病中的研究。然而，如本综述所述，最近高度选择性的糜蛋白酶抑制剂的出现为这种酶途径在几种易发炎症性血管疾病中的作用提供了新的启示。考虑到越来越多的证据表明Ang II和ET-1在心血管疾病中存在显着相互作用，本综述将探讨糜酶在这两种肽的产生中的作用。糜蛋白酶依赖性的ET-1产生是否在心血管疾病中也起重要作用。

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