BACKGROUND: In addition to hypertension control, direct renin inhibition has been shown to exert direct beneficial effects on the heart in post-infarction cardiac remodeling. This study elucidates the possible contribution of mitochondria to the anti-hypertrophic effects of the direct renin inhibitor aliskiren in post-infarction heart failure complicated with diabetes in rats. METHODS: Diabetes was induced in male Sprague-Dawley rats by a single injection of streptozotocin (IP, 65 mg/kg body weight). After 7 days, the animals were randomly assigned to 4 groups: sham, heart failure, sham+aliskiren, and heart failure+aliskiren. Post-infarction HF was induced by coronary artery ligation for 4 weeks. RESULTS: showed that heart failure reduced ejection fraction and cardiac output by 41% (P<0.01) and 42% (P<0.05), respectively, compared to sham-operated hearts. Cardiac dysfunction was associated with suppressed state 3 respiration rates and respiratory control index in mitochondria, and increased mitochondrial permeability transition pore (PTP) opening. In addition, heart failure reduced expression of the major mitochondrial sirtuin, SIRT3 and increased acetylation of cyclophilin D, a regulatory component of the PTP. Aliskiren significantly improved cardiac function and abrogated mitochondrial perturbations. CONCLUSION: Our results demonstrate that aliskiren attenuates post-infarction remodeling which is associated with its beneficial effects on mitochondria.
BACKGROUND: In addition to hypertension control, direct renin inhibition has been shown to exert direct beneficial effects on the heart in post-infarction cardiac remodeling. This study elucidates the possible contribution of mitochondria to the anti-hypertrophic effects of the direct renin inhibitor aliskiren in post-infarction heart failure complicated with diabetes in rats. METHODS:Diabetes was induced in male Sprague-Dawley rats by a single injection of streptozotocin (IP, 65 mg/kg body weight). After 7 days, the animals were randomly assigned to 4 groups: sham, heart failure, sham+aliskiren, and heart failure+aliskiren. Post-infarction HF was induced by coronary artery ligation for 4 weeks. RESULTS: showed that heart failure reduced ejection fraction and cardiac output by 41% (P<0.01) and 42% (P<0.05), respectively, compared to sham-operated hearts. Cardiac dysfunction was associated with suppressed state 3 respiration rates and respiratory control index in mitochondria, and increased mitochondrial permeability transition pore (PTP) opening. In addition, heart failure reduced expression of the major mitochondrial sirtuin, SIRT3 and increased acetylation of cyclophilin D, a regulatory component of the PTP. Aliskiren significantly improved cardiac function and abrogated mitochondrial perturbations. CONCLUSION: Our results demonstrate that aliskiren attenuates post-infarction remodeling which is associated with its beneficial effects on mitochondria.
Authors: Scott D Solomon; Sung Hee Shin; Amil Shah; Hicham Skali; Akshay Desai; Lars Kober; Aldo P Maggioni; Jean L Rouleau; Roxzana Y Kelly; Allen Hester; John J V McMurray; Marc A Pfeffer Journal: Eur Heart J Date: 2011-02-10 Impact factor: 29.983
Authors: Peter M Abadir; D Brian Foster; Michael Crow; Carol A Cooke; Jasma J Rucker; Alka Jain; Barbara J Smith; Tyesha N Burks; Ronald D Cohn; Neal S Fedarko; Robert M Carey; Brian O'Rourke; Jeremy D Walston Journal: Proc Natl Acad Sci U S A Date: 2011-08-18 Impact factor: 11.205
Authors: T Ide; H Tsutsui; S Hayashidani; D Kang; N Suematsu; K Nakamura; H Utsumi; N Hamasaki; A Takeshita Journal: Circ Res Date: 2001-03-16 Impact factor: 17.367
Authors: Angela V Hafner; Jing Dai; Ana P Gomes; Chun-Yang Xiao; Carlos M Palmeira; Anthony Rosenzweig; David A Sinclair Journal: Aging (Albany NY) Date: 2010-12 Impact factor: 5.682
Authors: George A Porter; William R Urciuoli; Paul S Brookes; Sergiy M Nadtochiy Journal: Am J Physiol Heart Circ Physiol Date: 2014-04-18 Impact factor: 4.733
Authors: Xin Zhao; Poornima Balaji; Ronald Pachon; Daniella M Beniamen; Dorothy E Vatner; Robert M Graham; Stephen F Vatner Journal: Arterioscler Thromb Vasc Biol Date: 2015-09-03 Impact factor: 8.311
Authors: Xiaokan Zhang; Ruiping Ji; Xianghai Liao; Estibaliz Castillero; Peter J Kennel; Danielle L Brunjes; Marcus Franz; Sven Möbius-Winkler; Konstantinos Drosatos; Isaac George; Emily I Chen; Paolo C Colombo; P Christian Schulze Journal: Circulation Date: 2018-01-12 Impact factor: 29.690