Department of Cardiology, The Second Affiliated Hospital, Cardiovascular Key Laboratory of Zhejiang Province, College of Medicine, Zhejiang University Hangzhou, Zhejiang, China.
Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, U.S.A.
Biosci Rep. 2019 May 3;39(5). doi: 10.1042/BSR20182055. Print 2019 May 31.
Angiotensin (Ang) A is formed by the decarboxylation of the N terminal residue of AngII. The present study determined whether this one amino acid change impacted effects of AngII on abdominal aortic aneurysm (AAA) formation in mice. Computational analyses implicated that AngA had comparable binding affinity to both AngII type 1 and 2 receptors as AngII. To compare effects of these two octapeptides , male low-density lipoprotein receptor () or apolipoprotein E () deficient mice were infused with either AngII or AngA (1 μg/kg/min) for 4 weeks. While AngII infusion induced AAA consistently in both mouse strains, the equivalent infusion rate of AngA did not lead to AAA formation. We also determined whether co-infusion of AngA would influence AngII-induced aortic aneurysm formation in male mice. Co-infusion of the same infusion rate of AngII and AngA did not change AngII-induced AAA formation. Since it was reported that a 10-fold higher concentration of AngA elicited comparable vasoconstrictive responses as AngII, we compared a 10-fold higher rate (10 μg/kg/min) of AngA infusion into male mice with AngII (1 μg/kg/min). This rate of AngA led to abdominal aortic dilation in three of ten mice, but no aortic rupture, whereas the 10-fold lower rate of AngII infusion led to abdominal aortic dilation or rupture in eight of ten mice. In conclusion, AngA, despite only being one amino acid different from AngII, has diminished effects on aortic aneurysmal formation, implicating that the first amino acid of AngII has important pathophysiological functions.
血管紧张素（Ang）A 是通过血管紧张素 II（AngII）N 端残基的脱羧形成的。本研究旨在确定这一氨基酸变化是否会影响 AngII 对小鼠腹主动脉瘤（AAA）形成的作用。计算分析表明，AngA 与 AngII 型 1 和 2 受体的结合亲和力相当。为了比较这两种八肽的作用，雄性低密度脂蛋白受体（）或载脂蛋白 E（）缺陷型小鼠分别输注 AngII 或 AngA（1μg/kg/min）4 周。虽然 AngII 输注在两种小鼠品系中均一致地诱导 AAA，但等效的 AngA 输注率不会导致 AAA 形成。我们还确定了 AngA 的共输注是否会影响雄性 小鼠中 AngII 诱导的主动脉瘤形成。以相同的输注率共输注 AngII 和 AngA 并未改变 AngII 诱导的 AAA 形成。由于据报道，AngA 的浓度高 10 倍即可产生与 AngII 相当的血管收缩反应，我们比较了高 10 倍的 AngA 输注率（10μg/kg/min）与 AngII（1μg/kg/min）在雄性 小鼠中的作用。该 AngA 输注率导致 10 只小鼠中的 3 只出现腹主动脉扩张，但无主动脉破裂，而 AngII 输注率高 10 倍则导致 10 只小鼠中的 8 只出现腹主动脉扩张或破裂。总之，尽管 AngA 与 AngII 仅相差一个氨基酸，但对主动脉瘤形成的作用减弱，这表明 AngII 的第一个氨基酸具有重要的病理生理功能。
