title: Oleanolic acid alleviated pressure overload-induced cardiac remodeling.
abstract: Previous study has demonstrated that oleanolic acid (OA) possessing the anti-inflammatory and anti-oxidant properties blunted high-glucose-induced diabetic cardiomyopathy and ameliorated experimental autoimmune myocarditis in mice. However, little is known about its effects on pressure overload-induced cardiac remodeling. Herein, we investigated the effect of OA on cardiac remodeling and underlying mechanism. Mice, subjected to aortic banding (AB), were randomly assigned into control group and experimental group. OA premixed in diets was administered to mice after 3 days of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed after 8 weeks' treatment of OA. Histologic examination and molecular analyses were used to assess cardiac hypertrophy and tissue fibrosis. In addition, the inhibitory effects of OA on H9c2 cardiomyocytes and cardiac primary fibroblast responded to the stimulation of AngII were also investigated. OA ameliorated the systolic and diastolic dysfunction induced by pressure overload evidenced by echocardiography and catheter-based measurements. OA also decreased the mRNA expression of cardiac hypertrophy and fibrosis markers evidenced by RT-PCR. It has been shown in our study that pressure overload activated the phosphorylations of Akt, mTOR, p70s6k, S6, GSK3β, and FoxO3a, and treatment of OA attenuated the phosphorylation of these proteins. In addition, hypertrophy of cardiomyocytes and fibrosis markers induced by AngII was inhibited by OA in vitro. Our findings uncover that OA suppressed AB-induced cardiac hypertrophy, partly by inhibiting the activity of Akt/mTOR pathway, and suggest that treatment of OA may have a benefit on retarding the progress of cardiac remodeling under long terms of pressure overload.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Jiefang Road 238, Wuhan, 430060, China.
authors.forename: Hai-Han
authors.initials: HH
authors.lastname: Liao
authors.affiliation: Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Zhong Nan Hospital of Wuhan University, Wuhan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Jiefang Road 238, Wuhan, 430060, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Jiefang Road 238, Wuhan, 430060, China.
authors.forename: Zhen-Guo
authors.initials: ZG
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Jiefang Road 238, Wuhan, 430060, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Jiefang Road 238, Wuhan, 430060, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Cardiovascular Research Institute, Wuhan University, Jiefang Road 238, Wuhan, 430060, China.
authors.forename: Zhou-Yan
authors.initials: ZY
authors.lastname: Bian
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China. qztang@whu.edu.cn.|Cardiovascular Research Institute, Wuhan University, Jiefang Road 238, Wuhan, 430060, China. qztang@whu.edu.cn.
authors.forename: Qi-Zhu
authors.initials: QZ
authors.lastname: Tang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000473:pathology*; D004452:Echocardiography; D005355:Fibrosis / Q000235:genetics / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D006973:Hypertension / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000502:physiology; D009828:Oleanolic Acid / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001786:Blood Glucose; D012333:RNA, Messenger; D000804:Angiotensin II; D009828:Oleanolic Acid; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D005947:Glucose
keywords: Akt/mTOR; Cardiac hypertrophy; Fibrosis; Oleanolic acid