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Haptoglobin Genotype Is a Determinant of Iron, Lipid Peroxidation, and Macrophage Accumulation in the Atherosclerotic Plaque

Haptoglobin Genotype Is a Determinant of Iron, Lipid Peroxidation, and Macrophage Accumulation in... Haptoglobin Genotype Is a Determinant of Iron, Lipid Peroxidation, and Macrophage Accumulation in the Atherosclerotic Plaque Andrew P. Levy, Joanne E. Levy, Shiri Kalet-Litman, Rachel Miller-Lotan, Nina S. Levy, Roy Asaf, Julia Guetta, Chingwen Yang, K. Raman Purushothaman, Valentin Fuster, Pedro R. Moreno Objective—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 macrophage accumulation 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 (P0.008), lipid peroxidation (4-hydroxynonenal and ceroid) and macrophage accumulation http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arteriosclerosis, Thrombosis, and Vascular Biology Wolters Kluwer Health

Haptoglobin Genotype Is a Determinant of Iron, Lipid Peroxidation, and Macrophage Accumulation in the Atherosclerotic Plaque

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/lp/wolters-kluwer-health/haptoglobin-genotype-is-a-determinant-of-iron-lipid-peroxidation-and-OLC0Sod8BQ
ISSN
1079-5642
eISSN
1524-4636
DOI
10.1161/01.ATV.0000251020.24399.a2
pmid
17068284

Abstract

Haptoglobin Genotype Is a Determinant of Iron, Lipid Peroxidation, and Macrophage Accumulation in the Atherosclerotic Plaque Andrew P. Levy, Joanne E. Levy, Shiri Kalet-Litman, Rachel Miller-Lotan, Nina S. Levy, Roy Asaf, Julia Guetta, Chingwen Yang, K. Raman Purushothaman, Valentin Fuster, Pedro R. Moreno Objective—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 macrophage accumulation 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 (P0.008), lipid peroxidation (4-hydroxynonenal and ceroid) and macrophage accumulation

Journal

Arteriosclerosis, Thrombosis, and Vascular BiologyWolters Kluwer Health

Published: Jan 1, 2007

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