Nishimura H, Hoffmann S, Baltatu O, Sugimura K, Ganten D, Urata H
Max-Delbrück-Centrum for Molecular Medicine, Department of Hypertension Research, Berlin-Buck, Germany.
Kidney Int Suppl. 1996 Jun;55:S18-23.
Recent studies have provided evidence that the human cardiovascular tissues contain components of the renin-angiotensin system: angiotensinogen, renin, angiotensin I converting enzyme (ACE), chymase and angiotensin II (Ang II) receptors. In addition to ACE, a cardiac Ang II forming serine proteinase, human heart chymase, has been identified in the human left ventricle. Unlike rat heart, only a minor (approximately 11%) component of Ang II forming activity in the human left ventricle was due to ACE, since the majority (approximately 80%) of activity was due to chymase. Human heart chymase has been purified to homogeneity and characterized. Recently, the cDNA and gene for this enzyme have been cloned. Biochemical characterization revealed that heart chymase is the most efficient and specific Ang II forming enzyme described thus far. The different cellular and regional distribution of ACE and heart chymase in the heart as well as in blood vessels implies distinct pathophysiological roles for these two Ang II forming enzymes. Several reports indicate that ACE-independent Ang II formation appears to take place in hypoxic or ischemic heart or blood vessel in vivo and to be involved in vascular remodeling after balloon injury. Therefore, it is very important to clarify the detailed mechanisms of the tissue Ang II formation in humans and its contribution to the pathophysiological changes in cardiovascular disease. In this review, we review the pathophysiological roles of the two main Ang II forming enzymes, ACE and chymase, in cardiovascular homeostasis.
最近的研究已提供证据表明，人类心血管组织含有肾素-血管紧张素系统的成分：血管紧张素原、肾素、血管紧张素I转换酶（ACE）、糜酶和血管紧张素II（Ang II）受体。除ACE外，在人类左心室中已鉴定出一种形成心脏Ang II的丝氨酸蛋白酶——人心脏糜酶。与大鼠心脏不同，在人类左心室中，形成Ang II活性的仅一小部分（约11%）是由ACE引起的，因为大部分（约80%）活性是由糜酶引起的。人心脏糜酶已被纯化至同质并进行了特性鉴定。最近，该酶的cDNA和基因已被克隆。生化特性表明，心脏糜酶是迄今为止所描述的最有效且最具特异性的Ang II形成酶。ACE和心脏糜酶在心脏以及血管中的细胞和区域分布不同，这意味着这两种Ang II形成酶具有不同的病理生理作用。几份报告表明，不依赖ACE的Ang II形成似乎在体内缺氧或缺血的心脏或血管中发生，并参与球囊损伤后的血管重塑。因此，阐明人类组织中Ang II形成的详细机制及其对心血管疾病病理生理变化的作用非常重要。在本综述中，我们回顾了两种主要的Ang II形成酶ACE和糜酶在心血管稳态中的病理生理作用。
