CAVD arises from myofibroblast differentiation of VICs in response to paracrine action of stimuli TGF-β, and our data show that Ca2+ influx through CaV1.2 may be a key downstream step, because our in vivo CaV1.2 mouse models showed lesion development in the absence of any such exogenous paracrine stimuli and in the absence of the hypercholesterolemia stimulus commonly used in CAVD mouse models. Here, TGFB1 is linked to congenital bilateral aplasia of vas deferens from CFTR mutation.