An evolving story of angiotensin-II-forming pathways in rodents and humans.
An evolving story of angiotensin-II-forming pathways in rodents and humans.
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DOI：
10.1042/cs20130400
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Dell'italia LJ
中科院分区：
文献类型：
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作者：
Ferrario CM;Ahmad S;Nagata S;Simington SW;Varagic J;Kon N;Dell'italia LJ
从血管紧张素-(1-7) 在对抗血管紧张素 II 的血管收缩、增殖和促血栓形成作用中的生物学作用的表征中获得的经验教训，为更全面地探索血液和组织肾素血管紧张素系统在疾病过程中调节稳态及其改变状态的多种途径奠定了基础。本综述总结了通过表征十二肽血管紧张素-(1-12) 在心脏产生血管紧张素 II 中的表达和功能，对中间较短形式的血管紧张素原进行新探索所取得的进展。这些研究揭示了人类与啮齿动物在血管紧张素-(1-12) 代谢的酶途径方面存在显着差异。该研究的亮点包括证明在人左心房肌细胞和左心室组织中，血管紧张素-(1-12)可以通过食糜酶直接形成血管紧张素II，在难治性心房颤动受试者的心耳中存在血管紧张素-(1-12)和食糜酶的强烈表达，以及初步观察到 血管紧张素-(1-12) 在人左心耳中的表达。
Lessons learned from the characterization of the biological roles of angiotensin-(1-7) in opposing the vasoconstrictor, proliferative, and prothrombotic actions of angiotensin II created an underpinning for a more comprehensive exploration of the multiple pathways by which the blood and tissues renin angiotensin system regulates homeostasis and its altered state in disease processes. This review summarizes the progress that has been made in the novel exploration of intermediate shorter forms of angiotensinogen through the characterization of the expression and functions of the dodecapeptide angiotensin-(1-12) in the cardiac production of angiotensin II. The studies reveal significant differences in humans versus rodents regarding the enzymatic pathway by which angiotensin-(1-12) undergoes metabolism. Highlights of the research include the demonstration of chymase-direct formation of angiotensin II from angiotensin-(1-12) in human left atrial myocytes and left ventricular tissue, the presence of robust expression of angiotensin-(1-12) and chymase in the atrial appendage of subjects with resistant atrial fibrillation, and the preliminary observation of significantly higher angiotensin-(1-12) expression in human left atrial appendages.