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A mitochondrial‐targeting peptide (Bendavia) decreases apoptosis and suppresses cardiac fibrosis in the noninfarcted border zone of infarcted hearts (1154.3)
Author(s) -
Shi Jianru,
Dai Wangde,
Hale Sharon,
Kloner Robert
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1154.3
Subject(s) - tunel assay , apoptosis , fibrosis , ligation , cardiac function curve , myocardial fibrosis , medicine , ventricular remodeling , endocrinology , staining , chemistry , myocardial infarction , immunohistochemistry , andrology , cardiology , pathology , heart failure , biochemistry
Bendavia is a mitochondrial‐targeting peptide with cardioprotective properties. Apoptosis and cardiac fibrosis contribute to left ventricular remodeling in the post infarct state. We hypothesized that Bendavia decreases apoptosis and attenuates myocardial collagen deposition in the noninfarcted border zone (2 mm noninfarcted tissue on either side of scar). Starting 2 hours after left coronary artery ligation, rats were randomized to receive Bendavia (3 mg/kg/day), water or sham operation. At 6 weeks, TUNEL staining was performed to detect apoptosis. Picrosirius red staining and qRT‐PCR were used to analyze collagen deposition. TUNEL positive cells within the border zone were reduced by Bendavia (32 ± 3% of nuclei, n=12) vs the water group (41 ± 2%, n=12; p=0.029). Bendavia significantly suppressed collagen deposition, assessed by Picrosirius red staining, within the border zone (11 ± 1% of the area of border zone, n=28) vs water group (15 ± 1%, n=26; p=0.03). qRT‐PCR analysis showed that Col1a1, Col1a2 and Col3a1 gene expression were significantly increased by 4.76 fold, p=0.002, 2.85 fold, p=0.01 and 4.71 fold, p=0.019, respectively, in the water group vs sham. Importantly, Bendavia showed a trend of lowering these gene expression levels. We conclude that Bendavia decreases apoptosis and prevents cardiac fibrosis, which may have led to the preservation of cardiac function and structure.