RGS5 and triple-A syndrome: •Evaluation of normal aortic tissue demonstrated 11 VSMC-like clusters, including 9 VSMC subpopulations, one EC-like VSMC cluster, and one fibroblast-like cluster•Gene ontology (GO) analysis of DEGs showed functional diversity of the 9 VSMC subpopulations; pathway enrichment analysis revealed functional heterogeneity of VSMCs•RGS5, a regulator of G protein signaling molecules, was specifically elevated in the homeostasis associated VSMC subpopulation, which immunohistochemistry revealed RGS5 and Fn positive VSMCs were nearly absent in AAA tissue