Abstract 297: Haptoglobin Genotype is a Determinant of Oxidation and Inflammation in the Atherosclerotic Plaque
Introduction. Intraplaque hemorrhage increases the risk of plaque rupture and thrombosis. The release of hemoglobin (Hb) from extravasated erythrocytes at the site of hemorrhage leads to iron deposition, which may increase oxidation and inflammation in the atherosclerotic plaque. The haptoglobin (Hp) protein is critical for protection against Hb-induced injury. Two common alleles exist at the Hp locus and the Hp 2 allele has been associated with increased risk of myocardial infarction. We have demonstrated decreased anti-oxidative and anti-inflammatory activity for the Hp 2 protein. We tested the hypothesis that the Hp 2–2 genotype is associated with increased oxidative and inflammatory activity in atherosclerotic plaques.
Methods and Results The murine Hp gene is a type 1 Hp allele. We created a murine type 2 Hp allele and targeted its insertion to the Hp locus by homologous recombination. Atherosclerotic plaques from C57Bl/6 ApoE−/ − Hp 2–2 mice were associated with increased iron deposition (p=0.008), ceroid lipid peroxidation (p=0.05) and macrophage infiltration (p=0.03) as compared to plaques from C57Bl/6 Apo E−/− Hp 1–1 mice. Macrophage infiltration was correlated with lipid core areas in Hp 2–2 (r=0.57, p=0.01) but not in Hp 1–1 plaques (r=0.07, p=0.38).
Conclusions Atherosclerotic plaques from ApoE−/− Hp 2–2 mice are associated with increased iron deposition, lipid peroxidation and macrophage infiltration indicating that the Hp genotype may play a critical role in the oxidative and inflammatory response to intraplaque hemorrhage.