Journal of molecular and cellular cardiology · 2018
Mitochondrial fission protein, dynamin-related protein 1, contributes to the promotion of hypertensive cardiac hypertrophy and fibrosis in Dahl-salt sensitive rats.
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Hasan Prottoy, Saotome Masao, Ikoma Takenori, Iguchi Keisuke, Kawasaki Hideya, Iwashita Toshihide, Hayashi Hideharu, Maekawa Yuichiro
Аннотация
BACKGROUND: Hypertension promotes cardiac hypertrophy which finally leads to cardiac dysfunction. Although aberrant mitochondrial dynamics is known to be a relevant contributor of pathogenesis in heart disease, little is known about the relationship between mitochondrial dynamics and cardiac hypertrophy. We investigated the pathophysiological roles of Dynamin-related protein1 (Drp1, a mitochondrial fission protein) on the hypertensive cardiac hypertrophy.
METHODS & RESULTS: Dahl salt-sensitive rats were fed with a low-salt (0.3% NaCl) or a high-salt (8% NaCl) chow to promote hypertension with and without administration of mdivi1 (an inhibitor of Drp1: 1 mg/kg/every alternative day), and then the hypertensive cardiac hypertrophy was assessed. High-salt fed rats exhibited left ventricular hypertrophy (LVH), myocytes hypertrophy, and cardiac fibrosis, and mdivi-1 suppressed them without alteration of the blood pressure. Mdivi1 also reduced ROS production by hypertension, which subsequently suppressed the Ca2+-activated protein phosphatase calcineurin and Ca2+/calmodulin-dependent kinase II (CaMKII).
CONCLUSIONS: Our results suggest that Drp1 contributes to the pathogenesis of hypertensive cardiac hypertrophy via ROS production and the Drp1 suppression may be effective to prevent the hypertensive cardiac hypertrophy.
METHODS & RESULTS: Dahl salt-sensitive rats were fed with a low-salt (0.3% NaCl) or a high-salt (8% NaCl) chow to promote hypertension with and without administration of mdivi1 (an inhibitor of Drp1: 1 mg/kg/every alternative day), and then the hypertensive cardiac hypertrophy was assessed. High-salt fed rats exhibited left ventricular hypertrophy (LVH), myocytes hypertrophy, and cardiac fibrosis, and mdivi-1 suppressed them without alteration of the blood pressure. Mdivi1 also reduced ROS production by hypertension, which subsequently suppressed the Ca2+-activated protein phosphatase calcineurin and Ca2+/calmodulin-dependent kinase II (CaMKII).
CONCLUSIONS: Our results suggest that Drp1 contributes to the pathogenesis of hypertensive cardiac hypertrophy via ROS production and the Drp1 suppression may be effective to prevent the hypertensive cardiac hypertrophy.