Angiotensin-Converting Enzyme 2 Activation Is Not a Common Feature of Angiotensin-Converting Enzyme Inhibitory Peptides

作者：Z. Wang, Hongbing Fan, Xiaoyu Bao, Jianping Wu · 发表于：Journal of Agricultural and Food Chemistry · 年份：2023 · DOI：10.1021/acs.jafc.2c04211 · 被引用次数：24 · 研究领域：Protein Hydrolysis and Bioactive Peptides、Renin-Angiotensin System Studies、Neuropeptides and Animal Physiology

Angiotensin-converting enzyme (ACE) catalyzes the formation of angiotensin II (Ang II), a vasoconstrictor, whereas its homologue ACE2 degrades Ang II into angiotensin (1-7) (Ang (1-7)), a vasodilator. Given the similarities in structure and their interconnected roles in the regulation of cardiovascular system, this study aims to investigate if ACE-inhibitory (ACEi) peptides can also activate ACE2. About 200 potent ACEi peptides were subjected to molecular docking, 20 peptides were selected for cell and in vitro enzymatic activity studies, and 5 peptides were fed orally to spontaneously hypertensive rats at a dose of 15 mg/kg body weight/day for 7 days. Peptides IKW and RIY showed significant antihypertensive activity with activated circulating/aortic ACE2, circulating Ang (1-7), and decreased Ang II levels. IQY reduced blood pressure, increased Ang (1-7) level, but did not affect ACE and ACE2. Peptides MAW and MRW did not affect blood pressure, ACE, and ACE2. Our study showed that ACE2 activation is not a common feature of ACEi peptides.