Department of Surgery and Physiology-Pharmacology, Wake Forest School of Medicine, Winston Salem, NC, USA.
Department of Anesthesiology, Wake Forest School of Medicine, Winston Salem, NC, USA.
Mol Cell Endocrinol. 2021 Jun 1;529:111119. doi: 10.1016/j.mce.2020.111119. Epub 2020 Dec 10.
The identification of an alternate extended form of angiotensin I composed of the first twelve amino acids at the N-terminal of angiotensinogen has generated new knowledge of the importance of noncanonical mechanisms for renin independent generation of angiotensins. The human sequence of the dodecapeptide angiotensin-(1-12) [N-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Va-Ile-COOH] is an endogenous substrate that in the rat has been documented to be present in multiple organs including the heart, brain, kidney, gut, adrenal gland, and the bone marrow. Newer studies have confirmed the existence of Ang-(1-12) as an Ang II-forming substrate in the blood and heart of normal and diseased patients. Studies to-date document that angiotensin II generation from angiotensin-(1-12) does not require renin participation while chymase rather than angiotensin converting enzyme shows high catalytic activity in converting this tissue substrate into angiotensin II directly.
血管紧张素 I 的一种替代延伸形式的鉴定，该形式由血管紧张素原 N 端的前十二个氨基酸组成，这为肾素非依赖性血管紧张素生成的非典型机制的重要性提供了新知识。十二肽血管紧张素-(1-12)[N-天冬氨酸-精氨酸-缬氨酸-酪氨酸-异亮氨酸-组氨酸-脯氨酸-苯丙氨酸-组氨酸-亮氨酸-缬氨酸-异亮氨酸-COOH]的人序列是一种内源性底物，在大鼠中已被证明存在于多个器官中，包括心脏、大脑、肾脏、肠道、肾上腺和骨髓。更新的研究证实了 Ang-(1-12)作为正常和患病患者血液和心脏中形成 Ang II 的底物的存在。迄今为止的研究表明，血管紧张素 II 的生成不需要肾素参与，而糜酶而不是血管紧张素转换酶显示出将这种组织底物直接转化为血管紧张素 II 的高催化活性。
