Search

1. Metformin is one of the most commonly used drugs for the treatment of Type 2 diabetes. Accumulating evidence suggests that metformin also has cardioprotective effects. In the present study, we investigated the cardioprotective effects of metformin and the mechanisms involved. 2. A rat model of chronic heart failure was established by permanent left coronary artery occlusion. Heart failure rats were randomly divided into four groups: (i) a saline-treated group given 4 mL/kg day via intragastric gavage; (ii) a metformin-treated group, given 100 mg/kg metformin once daily via intragastric gavage; (iii) a group treated with 5 mg/kg 5′-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR), an AMP-activated protein kinase (AMPK) agonist, every second day; and (iv) a group treated with 100 mg/kg per day metformin + 20 mg/kg, i.p., compound C (an AMPK antagonist). After 4 weeks treatment, echocardiography was used to assess left ventricular (LV) dimensions and function. Expression of AMPK, endothelial nitric oxide synthase (eNOS) and transforming growth factor (TGF)-β1 was determined by reverse transcription-polymerase chain reaction and western blot analysis. 3. Metformin administration significantly improved cardiac function and LV remodelling, as evidenced by increases in LV systolic pressure and LV ejection fraction and decreases in LV end-diastolic diameter and LV end-systolic diameter. These beneficial effects of metformin were associated with increased AMPK and eNOS phosphorylation, as well as reductions in insulin, TGF-β1, basic fibroblast growth factor and tumour necrosis factor-α levels in the circulation and/or myocardium. 4. The results indicate that chronic low-dose metformin confers significant cardioprotective effects against chronic heart failure by activating the AMPK-eNOS pathway. [ABSTRACT FROM AUTHOR]

1. Inhibiting the renin–angiotensin–aldosterone system prevents left ventricular (LV) remodelling after myocardial infarction (MI). 2. The present study was designed to assess the effects of a combination of perindopril and losartan on LV remodelling, cardiac function and serum procollagen type III amino terminal peptide (PIIINP) levels in patients with acute MI. 3. Patients with anterior MI were divided into three groups: (i) MI + perindopril; (ii) MI + losartan; and (iii) MI + perindopril + losartan. After successful intervention therapy, perindopril (2–4 mg daily), losartan potassium (25–50 mg daily) or their combination were administered. All patients received aspirin, clopidogrel and statins, and some patients were given beta-blockers, nitrate and a platelet glycoprotein IIb/IIIa receptor antagonist. Three months later, LV dimensions and LV ejection fraction (LVEF) were measured by ultrasonography. Plasma B-type natriuretic peptide (BNP), serum C-reactive protein (CRP) and PIIINP levels were evaluated using enzyme-linked immunosorbent assay or radioimmunoassay. 4. The baseline characteristics of the three groups were the same. Three months after the initiation of therapy, all patients showed decreased CRP, increased BNP and PIIINP levels and LV dilation and dysfunction. Compared with the two monotherapy groups, patients in the combination group showed significantly lower CRP, BNP and PIIINP levels, less LV dilation and higher LVEF. Serum PIIINP levels were positively correlated with CRP levels ( r = 0.597; P < 0.01) and LV end-diastolic volume index ( r = 0.543; P < 0.01) and were negatively correlated with LVEF ( r = –0.565; P < 0.01). 5. For patients with acute MI, combination treatment with perindopril and losartan significantly inhibited LV remodelling and improved LV function. Inhibition of myocardial interstitial fibrosis may be part of the underlying mechanism. [ABSTRACT FROM AUTHOR]