Our findings show that during WTD-induced hypercholesterolemia, deficiency of Abca1- and Abcg1-mediated cholesterol efflux pathways in SMCs increases α1-AR–mediated vasoconstriction, α1-AR–dependent urinary bladder distension, and bladder SMC transdifferentiation into Lgals3+ SMCs, macrophage-like and fibroblast-like cells, accompanied by increased collagen deposition and inflammatory gene expression. This evidence concerns the gene LGALS3 and familial hypercholesterolemia.