title: Bendavia, a mitochondria-targeting peptide, improves postinfarction cardiac function, prevents adverse left ventricular remodeling, and restores mitochondria-related gene expression in rats.
abstract: AB We evaluated the post-myocardial infarction (MI) therapeutic effects of Bendavia. Two hours after coronary artery ligation, rats were randomized to receive chronic Bendavia treatment (n = 28) or water (n = 26). Six weeks later, Bendavia significantly reduced scar circumference (39.7% +/- 2.2%) compared with water treatment (47.4% +/- 0.03%, P = 0.024) and reduced left ventricular (LV) volume by 8.9% (P = 0.019). LV fractional shortening was significantly improved by Bendavia (28.8% +/- 1.7%) compared with water treatment (23.8% +/- 1.8%, P = 0.047). LV ejection fraction was higher with Bendavia (55.3% +/- 1.4%) than water treatment (49.3% +/- 1.4%, P = 0.005). Apoptosis, within the MI border zone, was significantly less in the Bendavia group (32% +/- 3%, n = 12) compared with the water group (41% +/- 2%, n = 12; P = 0.029). Bendavia reversed mitochondrial function-related gene expression in the MI border, which was largely reduced in water-treated rats. Bendavia improved complex-I and -IV activity, and reduced production of reactive oxygen species and cytosolic cytochrome c level in the peri-infarcted region. Bendavia improved post-MI cardiac function, prevented infarct expansion and adverse LV remodeling, and restored mitochondria-related gene expression, complex-I and -IV activity, and reduced reactive oxygen species and cardiomyocyte apoptosis in the noninfarcted MI border.
authors.forename: Wangde
authors.initials: W
authors.lastname: Dai
authors.forename: Jianru
authors.initials: J
authors.lastname: Shi
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hale
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kloner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D042967:Electron Transport Complex I / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D009842:Oligopeptides; D017382:Reactive Oxygen Species; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; D045304:Cytochromes c; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I