title: AVE 3085, a novel endothelial nitric oxide synthase enhancer, attenuates cardiac remodeling in mice through the Smad signaling pathway.
abstract: AVE 3085 is a novel endothelial nitric oxide synthase enhancer. Although AVE 3085 treatment has been shown to be effective in spontaneously restoring endothelial function in hypertensive rats, little is known about the effects and mechanisms of AVE 3085 with respect to cardiac remodeling. The present study was designed to examine the effects of AVE 3085 on cardiac remodeling and the mechanisms underlying the effects of this compound. Mice were subjected to aortic banding to induce cardiac remodeling and were then administered AVE 3085 (10 mg kg day(-1), orally) for 4 weeks. At the end of the treatment, the aortic banding-treated mice exhibited significant elevations in cardiac remodeling, characterized by an increase in left ventricular weight relative to body weight, an increase in the area of collagen deposition, an increase in the mean myocyte diameter, and increases in the gene expressions of the hypertrophic markers atrial natriuretic peptide (ANP) and β-MHC. These indexes were significantly decreased in the AVE 3085-treated mice. Furthermore, AVE 3085 treatment reduced the expression and activation of the Smad signaling pathway in the aortic banding-treated mice. Our data showed that AVE 3085 attenuated cardiac remodeling, and this effect was possibly mediated through the inhibition of Smad signaling.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University and Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, PR China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University and Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, PR China.
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University and Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, PR China.
authors.forename: Cong
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University and Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, PR China.
authors.forename: Anli
authors.initials: A
authors.lastname: Tang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University and Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, PR China.
authors.forename: Yuedong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Class 3 of Year 2011, Faculty of Clinical Medicine (Eight-year Programme), Zhongshan School of Medicine, Sun Yat-sen University, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University and Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, PR China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University and Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, PR China. Electronic address: hejiangui@163.com.
authors.forename: Jiangui
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University and Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, PR China. Electronic address: ylinter@163.com.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000737:chemistry; D052117:Benzodioxoles / Q000737:chemistry* / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D015150:Echocardiography, Doppler; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D007189:Indans / Q000737:chemistry* / Q000494:pharmacology; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D011312:Pressure; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: C528910:2,2-difluorobenzo(1,3)dioxole-5-carboxylic acid indan-2-ylamide; D052117:Benzodioxoles; D005819:Genetic Markers; D007189:Indans; D012333:RNA, Messenger; D051785:Smad Proteins; D009320:Atrial Natriuretic Factor; D003094:Collagen; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: AVE 3085; Cardiac remodeling; Pressure overload; Smad signaling; eNOS