title: Angiotensin IV protects against angiotensin II-induced cardiac injury via AT4 receptor.
abstract: Angiotensin II (Ang II) is an important regulator of cardiac function and injury in hypertension. The novel Ang IV peptide/AT4 receptor system has been implicated in several physiological functions and has some effects opposite to those of Ang II. However, little is known about the role of this system in Ang II-induced cardiac injury. Here we studied the effect of Ang IV on Ang II-induced cardiac dysfunction and injury using isolated rat hearts, neonatal cardiomyocytes and cardiac fibroblasts. We found that Ang IV significantly improved Ang II-induced cardiac dysfunction and injury in the isolated heart in response to ischemia/reperfusion (I/R). Moreover, Ang IV inhibited Ang II-induced cardiac cell apoptosis, cardiomyocyte hypertrophy, and proliferation and collagen synthesis of cardiac fibroblasts; these effects were mediated through the AT4 receptor as confirmed by siRNA knockdown. These findings suggest that Ang IV may have a protective effect on Ang II-induced cardiac injury and dysfunction and may be a novel therapeutic target for hypertensive heart disease.
authors.affiliation: The Key Laboratory of Remodeling-related Cardiovascular Diseases, Department of Pathology School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Zeng
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
authors.forename: Li-Ke
authors.initials: LK
authors.lastname: Zhang
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Dong
authors.forename: Shubin
authors.initials: S
authors.lastname: Guo
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects*; D006984:Hypertrophy; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology
chemical_list: C090830:AT4 receptor; D034741:RNA, Small Interfering; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-