Metformin prevents the development of chronic heart failure in the SHHF rat model.

Abstract:

:Insulin resistance is a recently identified mechanism involved in the pathophysiology of chronic heart failure (CHF). We investigated the effects of two insulin-sensitizing drugs (metformin and rosiglitazone) in a genetic model of spontaneously hypertensive, insulin-resistant rats (SHHF). Thirty SHHF rats were randomized into three treatment groups as follows: 1) metformin (100 mg/kg per day), 2) rosiglitazone (2 mg/kg per day), and 3) no drug. Ten Sprague-Dawley rats served as normal controls. At the end of the treatment period (12 months), the cardiac phenotype was characterized by histology, echocardiography, and isolated perfused heart studies. Metformin attenuated left ventricular (LV) remodeling, as shown by reduced LV volumes, wall stress, perivascular fibrosis, and cardiac lipid accumulation. Metformin improved both systolic and diastolic indices as well as myocardial mechanical efficiency, as shown by improved ability to convert metabolic energy into mechanical work. Metformin induced a marked activation of AMP-activated protein kinase, endothelial nitric oxide synthase, and vascular endothelial growth factor and reduced tumor necrosis factor-α expression and myocyte apoptosis. Rosiglitazone did not affect LV remodeling, increased perivascular fibrosis, and promoted further cardiac lipid accumulation. In conclusion, long-term treatment with metformin, but not with rosiglitazone, prevents the development of severe CHF in the SHHF model by a wide-spectrum interaction that involves molecular, structural, functional, and metabolic-energetic mechanisms.

journal_name

Diabetes

journal_title

Diabetes

authors

Cittadini A,Napoli R,Monti MG,Rea D,Longobardi S,Netti PA,Walser M,Samà M,Aimaretti G,Isgaard J,Saccà L

doi

10.2337/db11-1132

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

944-53

issue

4

eissn

0012-1797

issn

1939-327X

pii

db11-1132

journal_volume

61

pub_type

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