Metformin Inhibits Isoproterenol-induced Cardiac Hypertrophy in Mice
- Metformin Inhibits Isoproterenol-induced Cardiac Hypertrophy in Mice
- 박소영; 차혜나; 최정현[최정현]; 김용운; 김종연; 안면환
- ACTIVATED PROTEIN-KINASE; LEFT-VENTRICULAR HYPERTROPHY; NITRIC-OXIDE; HEART-FAILURE; DIABETIC-PATIENTS; UP-REGULATION; RAT-HEART; MECHANISMS; OVEREXPRESSION; FIBROSIS
- Issue Date
- KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
- KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY, v.14, no.6, pp.377 - 384
- The present study examined whether metformin treatment prevents isoporterenol-induced cardiac hypertrophy in mice. Chronic subcutaneous infusion of isoproterenol (15 mg/kg/24 h) for 1 week using an osmotic minipump induced cardiac hypertrophy measured by the heart-to-body weight ratio and left ventricular posterior wall thickness. Cardiac hypertrophy was accompanied with increased interleukin-6 (IL-6), transforming growth factor (TGF)-beta, atrial natriuretic peptide (ANP), collagen I and III, and matrix metallopeptidase 2 (MMP-2). Coinfusion of metformin (150 mg/kg/24 h) with isoproterenol partially inhibited cardiac hypertrophy that was followed by reduced IL-6, TGF-beta, ANP, collagen I and III, and MMP-2. Chronic subcutaneous infusion of metformin did not increase AMP-activated protein kinase (AMPK) activity in heart, although acute intraperitoneal injection of metformin (10 mg/kg) increased AMPK activity. Isoproterenol increased nitrotyrosine levels and mRNA expression of antioxidant enzyme glutathione peroxidase and metformin treatment normalized these changes. These results suggest that metformin inhibits cardiac hypertrophy through attenuating oxidative stress.
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