Rapamycin reduces mineral density and promotes beneficial vascular remodeling in a murine model of severe medial arterial calcification

Peripheral artery disease (PAD) is associated with medial arterial calcification (MAC), which involves calcification of arterial elastic fibers and smooth muscle cells (SMCs). Matrix GLA protein (MGP) inhibits vascular calcification, and Mgp −/− mice develop severe MAC. Using this model, we found rapamycin (RAPA) prolonged lifespan, reduced arterial mineral density, maintained SMC contractile phenotype, and improved vessel structure, though calcification volume remained unchanged. Findings highlight rapamycin’s potential for vascular remodeling in MAC.