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Role of ACE2 in the Cardioprotective Effects of Angiotensin II Type 2 Receptors
Author(s) -
Zhu Liping,
Xu Jiang,
Harding Pamela,
Yang XiaoPing
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1207.6
Subject(s) - cardioprotection , angiotensin ii , medicine , endocrinology , receptor , chemistry , angiotensin converting enzyme 2 , antagonist , renin–angiotensin system , receptor antagonist , myocardial infarction , disease , covid-19 , blood pressure , infectious disease (medical specialty)
Blockade of angiotensin II (Ang II) type 1 receptors with angiotensin receptor blockers (ARBs) activates the Ang II type 2 receptors (AT 2 ) and also increases angiotensin‐converting enzyme 2 (ACE2) expression and Ang 1–7 levels. However, it is not known whether activation of AT 2 and ACE2 are synergistically associated to exert cardioprotection. We hypothesize that activation of AT 2 increases the expression and activity of ACE2, leading to cardioprotection. Transgenic mice with cardiac overexpression of AT 2 (Tg‐AT 2 ) were subjected to myocardial infarction (MI) for 12 weeks. We found that Tg‐AT 2 mice had cardiac ACE2 protein expression 2.36±0.07‐fold higher than the wild‐type (WT) controls, associated with better preserved cardiac function compared with WT controls (ejection fraction: 41.6±2.3% vs 27.6±1.8%). In AT 2 ‐stimulated coronary artery endothelial cells, ACE2 protein expression was increased by 1.79±0.04‐fold and ACE2 activity was enhanced from 0.61± 0.05 (basal) to 0.95±0.03 pg/μl/h/μg protein. These effects were blunted by AT 2 antagonist. Furthermore, activation of AT 2 increased cGMP by 1.71±0.12‐fold, which was diminished by Mas receptors antagonist. AT 2 activation also increased Ang 1–7 from 0.1±0.05 (basal) to 15.6±0.5 (pg/ml/μg protein) and this effect was diminished by the AT 2 antagonist. Our data suggest that the cardioprotective effects of AT 2 is in part mediated via activation of ACE2, enhancing the release of Ang 1–7 and leading to cardioprotection.