Pregnancy-associated plasma protein-A in atherosclerosis: Molecular marker, mechanistic insight, and therapeutic target

Abstract Pregnancy-associated plasma protein-A (PAPP-A), a member of the metzincin metalloproteinase superfamily, can enhance local insulin-like growth factor (IGF) bioavailability through proteolytic cleavage of three IGF binding proteins. In patients with coronary atherosclerosis disease (CAD), elevated PAPP-A levels are significantly associated with a higher risk of cardiovascular events. Accumulating evidence indicates that this protease exerts a proatherogenic effect by altering a variety of pathological processes involved in atherosclerosis, including lipid accumulation, vascular inflammation, endothelial dysfunction, vascular smooth muscle cell proliferation and migration, plaque stability, and thrombus formation. Moreover, blockade of its proteolytic activity by stanniocalcin or microRNAs is protective against atherosclerosis development. In this review, we summarized the latest advances regarding the roles of PAPP-A in the pathogenesis of atherosclerosis with an emphasis on its diagnostic and prognostic values in CAD.