Conditional down-expression of the mineralocorticoid receptor in mouse cardiomyocytes induced severe heart failure and cardiac fibrosis, which were fully reversible upon suppression of the antisense mRNA.
Does conditional knock-down of the mineralocorticoid receptor in cardiomyocytes induce reversible heart failure and cardiac fibrosis in mice?
Conditional knock-down of the mineralocorticoid receptor specifically in cardiomyocytes induces severe, reversible heart failure and cardiac fibrosis in mice, highlighting a critical physiological role for cardiac MR independent of circulating aldosterone levels.
Absolute Event Rate: 69% vs 78%
p-value: p=<0.05
Cardiac failure is a common feature in the evolution of cardiac disease. Among the determinants of cardiac failure, the renin-angiotensin-aldosterone system has a central role, and antagonism of the mineralocorticoid receptor (MR) has been proposed as a therapeutic strategy. In this study, we questioned the role of the MR, not of aldosterone, on heart function, using an inducible and cardiac-specific transgenic mouse model. We have generated a conditional knock-down model by expressing solely in the heart an antisense mRNA directed against the murine MR, a transcription factor with unknown targets in cardiomyocytes. Within 2-3 mo, mice developed severe heart failure and cardiac fibrosis in the absence of hypertension or chronic hyperaldosteronism. Moreover, cardiac failure and fibrosis were fully reversible when MR antisense mRNA expression was subsequently suppressed.
Beggah et al. (Tue,) conducted a other in Cardiac fibrosis and heart failure. Conditional expression of MR antisense mRNA vs. Control littermates was evaluated on Left ventricular ejection fraction (EF) (p=<0.05). Conditional down-expression of the mineralocorticoid receptor in mouse cardiomyocytes induced severe heart failure and cardiac fibrosis, which were fully reversible upon suppression of the antisense mRNA.