A Transgenic Platform for Testing Drugs Intended for Reversal of Cardiac Remodeling Identifies a Novel 11βHSD1 Inhibitor Rescuing Hypertrophy Independently of Re-Vascularization
Figure 5
Pharmacological inhibition of 11β HSD1 reverses cardiac hypertrophy in a model of Isoproterenol-induced heart failure.
(A) Fractional shortening measured in mice treated for 5 weeks with Isoproterenol(ISO-5w) alone, Isoproterenol together with 11β-HSD1 inhibitor (ISO+CpdA-5w) or treated with Isoproterenol alone for 3 weeks and by Isoproterenol and 11β-HSD1 inhibitor for an additional 2 weeks (ISO-3w→ISO+CpdA-2w). N = 5–7 mice per treatment group. (B) End diastolic LV diameter in the same mice as in A. (C) Representative axial sections at the level of the papillary muscle. (D) Cardiomyocyte area standardized to littermate controls. N = 5–7 mice and 25–30 cardiomyocytes were analyzed for each section. (E) Heart to body weight ratio. (F) MVD. N = 5–7 mice per treatment group and 3 HPFs were measured for each mouse. * P<0.05, ** P<0.001, NS = not statistically significant.