Accelerated atherosclerosis in individuals with the haptoglobin 2-2 genotype and diabetes is mediated by macrophage lysosomal injury and apoptosis

Abstract

Background: There exists a common functional allelic polymorphism in the Haptoglobin (Hp) gene which has been associated with the risk of cardiovascular disease in individuals with diabetes mellitus (DM). In the atherosclerotic plaque, the CD163 macrophage Hp-hemoglobin (Hb) receptor is responsible for clearing Hb released after intraplaque hemorrhage. In DM, the Hp 2 allele protein product is defective in its Hb scavenging properties and has been associated with increased iron in the atherosclerotic plaque.