BioProject

To find which genes were significantly modulated by Valsartan in non-infarcted left ventricle, 4 weeks after coronary artery ligation, and to correlate emerging modulated pathways with histology and cardiac magnetic resonance (CMR) imaging. More...

To find which genes were significantly modulated by Valsartan in non-infarcted left ventricle, 4 weeks after coronary artery ligation, and to correlate emerging modulated pathways with histology and cardiac magnetic resonance (CMR) imaging. The goal was to validate the estimation of the systolic dysfunction and of the regions preserved by pharmacological treatment performed with a CMR index. Title of the associated submitted paper: Evaluation of left ventricle function by regional fractional area change (RFAC) in a mouse model of myocardial infarction secondary to Valsartan treatment. Abstract: Purpose: Left ventricle (LV) regional fractional area change (RFAC) measured by cardiac magnetic resonance (CMR) allows the non-invasive localization and quantification of the extent of myocardial infarction (MI), and could be applied to assess the effectiveness of pharmacological or regenerative therapies. Here we investigate the ability of RFAC to identify regional dysfunction and discriminate the effect of pharmacological treatment with valsartan, a selective antagonist of angiotensin II type 1 receptor, in a model of MI. Methods: C57BL/6N mice, undergoing coronary artery ligation, were divided into two groups: untreated (MI) or treated with Valsartan (MI+Val). Sham-operated mice were used as a control. Cardiac dimensions and function were assessed at baseline, 24 hours, 1 and 4 weeks post surgery by CMR and echocardiography. At sacrifice histology and whole-genome gene expression profiling were performed. Results: RFAC was able to detect significant differences between treatment groups whereas the global ejection fraction was not. RFAC showed greater loss of contractility in remote non-infarcted myocardium in MI group than in MI+Val group. Consistently, in the same region MI+Val mice showed reduced myocyte hypertrophy, fibroblast proliferation, and fibrosis and modulation of target genes; in addition, left atrium volumes, appendage length and duct contractility were preserved. Conclusion: In this study, RFAC effectively estimated the degree of systolic dysfunction and discriminated the regions preserved by pharmacological treatment. RFAC index is a promising tool to monitor changes in LV contractility and to assess the effectiveness of therapeutic regimens in clinical settings. Overall design: MI was induced by left anterior descending (LAD) coronary artery ligation. Mice were randomized to 2 experimental groups: infarcted only animals (MI, n=6) and treated animals with Valsartan 1 mg/Kg/die in drinking water (MI+Val, n=5). As control of surgery procedure, sham operated mice underwent thoracotomy without LAD coronary artery ligation (n=6). For transcriptome analysis, 4 weeks after surgery hearts were perfused with PBS and the portion of the non-infarcted wall corresponding to the posterior and inferior sectors was collected in RNAlater (Life Technologies) and stored at -80°C. Less...