Stabilization of Hypoxia-inducible Factor by DMOG Inhibits Development of Chronic Hypoxia–Induced Right Ventricular Remodeling. Issue 1 (January 2016)

• Record Type: Journal Article
• Authors: Zhang, Sen; Ma, Kai; Liu, Yiwei; Pan, Xiangbin; Chen, Qiuming; Qi, Lei; Li, Shoujun
• Is Part Of: Journal of cardiovascular pharmacology. Volume 67:Issue 1(2016)
• Publication Date: 2016-01
• Subjects: DMOG -- HIF-1α -- chronic hypoxia -- right ventricular -- hypertrophy -- remodeling; Cardiovascular Diseases -- drug therapy -- Periodicals; Cardiovascular System -- drug effects -- Periodicals; Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular agents; Cardiovascular pharmacology; Periodicals; 615.7105
• DOI: 10.1097/FJC.0000000000000315
• Languages: English
• ISSNs: 0160-2446

Abstract

Abstract : Background: One important determinant of longevity in congenital heart disease is right ventricular (RV) function, and this is especially true in cyanotic congenital heart disease. However, there is a paucity of data concerning right ventricular remodeling (RVR) in the setting of chronic hypoxia. Dimethyloxalylglycine (DMOG) is a competitive inhibitor of hypoxia-inducible factor (HIF)-hydroxylated prolyl hydroxylase and has been shown to play an important role against ischemia–reperfusion myocardial injury. Methods: We tested the hypothesis that DMOG prevents the development RVR after chronic hypoxia exposure. Rats were injected with saline or DMOG and exposed to room air or continued hypoxia for 4 weeks. In addition, we explored the response of myocardial erythropoietin and its receptor to hypoxic exposure. Results: Treatment with DMOG attenuated myocardial fibrosis, apoptosis, and oxidative stress, which lead to enhanced RV contractile function. As an endpoint of HIF-dependent cardioprotection, a novel pathway in which nuclear factor kappa B links HIF-1 transcription was defined. Conclusions: This study supports a role for HIF-1 stabilizers in the treatment of RVR and brings into question the commonly held concept that RVR follows a linear relationship with increased RV afterload. Abstract : Supplemental Digital Content is Available in the Text.