A Transgenic Platform for Testing Drugs Intended for Reversal of Cardiac Remodeling Identifies a Novel 11βHSD1 Inhibitor Rescuing Hypertrophy Independently of Re-Vascularization
Figure 6
Rescue of hypertrophy is associated with reversing the hypertrophic gene signature, including of the Myosin heavy chain isoform shift.
(A) Real time PCR results of selected genes in control and dTg (dTg ON) mice after 12 weeks of sVEGF-R1 induction, with or without treatment in the last 3 weeks. Treatment groups included either 11βHSD1 inhibitor (Roche Cpd A), Enalapril (ACE-I), Pioglitazone (PIO) or VEGF-driven neo-vascularization by sVEGF-R1 withdrawal (dTg ON>OFF). Results are normalized relative to litter-mate controls (designated as 1). N = 4-6 mice. Genes examined: Brain naturetic peptide (BNP). Glucose transporter 1 (Glut1) and Periostin. See text for further elaboration. (B) Real time PCR results of MyHCβ and MyHCα in control and dTg (dTg ON) mice after 12 weeks of sVEGF-R1 induction, with or without treatment in the last 3 weeks. N = 4–6 mice. Quantification (right diagram in B) and representative images (C) of immunohistochemistry for MyHCβ in the same mice as in B, depicting MyHCβ protein level elevation in dTg mice and rescue by both treatments. Scale bars: 50 µm. * P<0.05, ** P<0.001, NS = not statistically significant.