Improvement of cardiovascular remodelling by chymase inhibitor
Improvement of cardiovascular remodelling by chymase inhibitor
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食糜酶抑制剂改善心血管重塑
DOI：
10.1111/1440-1681.12549
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Jin D.
中科院分区：
文献类型：
--
作者：
Takai S;Jin D.
Chymase已被确定为心血管组织中发现的血管紧张素II形成酶。血管紧张素II不仅参与血压的调节，还参与心血管重构的进程。有趣的是，乳糜酶抑制剂在不降低血压的情况下防止心血管重塑。乳糜酶抑制剂不影响血压的原因可能取决于体内乳糜酶的定位。在正常组织中，乳糜酶储存在肥大细胞颗粒中，不具有酶促功能；然而，在受损组织中，溶酶在其从颗粒中释放后立即表现出酶活性。切酶还激活转化生长因子β和基质金属蛋白酶- 9，这两种酶都参与心血管重构，它们的酶功能也只在受损组织中被观察到。在高血压、糖尿病和高胆固醇血症的动物模型中，乳糜酶抑制剂改善心血管重塑，但不影响包括血压在内的一般循环。因此，我们认为乳糜酶可能是预防心血管疾病的重要靶点。
Chymase has been identified as an angiotensin II‐forming enzyme found in cardiovascular tissues. Angiotensin II is involved not only in the regulation of blood pressure, but also in the progression of cardiovascular remodelling. Interestingly, chymase inhibitors prevent cardiovascular remodelling without lowering blood pressure. The reason why chymase inhibitors do not affect blood pressure may depend on the localization of chymasein vivo. In normal tissues, chymase is stored in mast cell granules and has no enzymatic function; whereas, in damaged tissues, chymase exhibits enzymatic activity immediately following its release from the granules. Chymase also activates transforming growth factor‐βand matrix metalloproteinase‐9, both of which are involved in cardiovascular remodelling, and their enzymatic functions are also observed only in damaged tissues. In animal models of hypertension, diabetes and hypercholesterolaemia, chymase inhibitors improve cardiovascular remodelling without a general circulatory effect, including blood pressure. Thus, it is proposed that chymase is a potentially important target for preventing cardiovascular diseases.