Accordingly, loss of eNOS aggravated aortic valve calcification in mice model of CAVD, whilst reinstating nitric oxide (NO) signaling effectively attenuated osteogenic differentiation of VICs, strongly indicating a protective role of VECs-derived NO in CAVD (El et al., 2014; Majumdar et al., 2021). The gene discussed is NOS3; the disease is congenital bilateral aplasia of vas deferens from CFTR mutation.