However, the activity of the angiotensin-converting enzyme 2 was associated with the degree of calcification but not the severity of stenosis (Ramchand et al., 2020), indicating that further research was urgent for the role of the valvular renin-angiotensin system in CAVD pathogenesis beyond its effects on hypertension. Here, REN is linked to congenital bilateral aplasia of vas deferens from CFTR mutation.