Active renin exclusively controls the first rate limiting step in RAAS cascade i.e. conversion of angiotensinogen to angiotensin I. The early (at 7 weeks) and sustained elevation of active renin (13 weeks) observed in female mice with DCM may have contributed to the more severe interstitial fibrosis, ventricular dilation, HF and greater mortality observed in these mice [24,42]. This evidence concerns the gene REN and familial dilated cardiomyopathy.