A novel experimental system for testing remodeling reversing drugs shows RAAS inhibition reverses remodeling independently of improving perfusion.

<p>(<i>A</i>) Schematic representation of the transgenic lines used in the bi-transgenic inducible system. (<i>B</i>) Quantification of micro-vessels density (MVD), expressed as the number of endothelial cell-specific lectin-positive capillaries per high-power field (HPF). MVD was determined after 12 weeks of sVEGF-R1 induction during the last 3 weeks of which some of the dTg mice were treated with Enalapril (ENA) or Aliskiren (Alis) or both. N = 6–16 mice per treatment group and 3 HPFs were measured for each mouse. (<i>C</i>) Fractional shortening measured by M-mode Echocardiography in mice treated as in B. N = 5 mice. (<i>D</i>) End diastolic LV diameter measured by M-mode Echocardiography. (<i>E</i>) Representative axial sections at the level of the papillary muscle showing drug-induced reduction of LV size. (<i>F</i>) Cardiomyocyte area was measured from H&E-stained sections using Image J software and was standardized to littermate controls. N = 6-12 mice and 25-30 cardiomyocytes were analyzed for each section. (<i>G</i>) Heart to body weight ratio in the same mice shown in F. * <i>P</i><0.05, ** <i>P</i><0.001, NS = not statistically significant.