OBJECTIVES: We sought to test the hypothesis that haptoglobin (Hp) genotype is a determinant of the amount of iron in the atherosclerotic plaque. BACKGROUND: In atherosclerotic lesions, intraplaque hemorrhage releases free hemoglobin (Hb), whose incorporated iron can act as an oxidant and inflammatory stimulus. These effects are antagonized by Hp, which binds free Hb and facilitates its clearance from the plaque. The Hp gene has 2 alleles (1 and 2), giving rise to 3 genotypes: Hp 1-1, Hp 2-1, and Hp 2-2. We previously hypothesized that Hp 2-2 individuals with diabetes mellitus (DM) have impaired clearance of Hb and its iron cargo from the plaque. METHODS: We identified the presence or absence of Perl's iron stain in 189 plaques obtained from 37 decedents at autopsy. RESULTS: Among DM, the prevalence of Perl's iron stain was increased in Hp 2-2 compared with that seen in Hp 1-1 or 2-1 (46.2% vs. 11.8%). After accounting for the within-decedent correlation of plaques, the prevalence ratio of Perl's iron stain associated with Hp 2-2 was 3.97 (95% confidence interval: 1.38 to 11.5; p = 0.025). In non-DM plaques, there was a nonsignificant trend towards a higher prevalence of iron staining in Hp 2-2 compared with that in Hp 1-1 or 2-1 (26.8% vs. 11.1%; prevalence ratio =2.40 [95% confidence interval: 0.81 to 7.09]; p = 0.114). CONCLUSIONS: These data support an impaired clearance of Hb from plaques in Hp 2-2 individuals, particularly in DM. The higher prevalence of plaque iron in Hp 2-2 DM individuals may contribute to the increased incidence of atherothrombotic events in these patients.
OBJECTIVES: We sought to test the hypothesis that haptoglobin (Hp) genotype is a determinant of the amount of iron in the atherosclerotic plaque. BACKGROUND: In atherosclerotic lesions, intraplaque hemorrhage releases free hemoglobin (Hb), whose incorporated iron can act as an oxidant and inflammatory stimulus. These effects are antagonized by Hp, which binds free Hb and facilitates its clearance from the plaque. The Hp gene has 2 alleles (1 and 2), giving rise to 3 genotypes: Hp 1-1, Hp 2-1, and Hp 2-2. We previously hypothesized that Hp 2-2 individuals with diabetes mellitus (DM) have impaired clearance of Hb and its iron cargo from the plaque. METHODS: We identified the presence or absence of Perl's iron stain in 189 plaques obtained from 37 decedents at autopsy. RESULTS: Among DM, the prevalence of Perl's iron stain was increased in Hp 2-2 compared with that seen in Hp 1-1 or 2-1 (46.2% vs. 11.8%). After accounting for the within-decedent correlation of plaques, the prevalence ratio of Perl's iron stain associated with Hp 2-2 was 3.97 (95% confidence interval: 1.38 to 11.5; p = 0.025). In non-DM plaques, there was a nonsignificant trend towards a higher prevalence of iron staining in Hp 2-2 compared with that in Hp 1-1 or 2-1 (26.8% vs. 11.1%; prevalence ratio =2.40 [95% confidence interval: 0.81 to 7.09]; p = 0.114). CONCLUSIONS: These data support an impaired clearance of Hb from plaques in Hp 2-2 individuals, particularly in DM. The higher prevalence of plaque iron in Hp 2-2 DM individuals may contribute to the increased incidence of atherothrombotic events in these patients.
Authors: Miriam Lipiski; Jeremy W Deuel; Jin Hyen Baek; Wolfgang R Engelsberger; Paul W Buehler; Dominik J Schaer Journal: Antioxid Redox Signal Date: 2013-03-28 Impact factor: 8.401
Authors: Xianling Wang; Jie Sun; Xihai Zhao; Daniel S Hippe; Thomas S Hatsukami; Jin Liu; Rui Li; Gador Canton; Yan Song; Chun Yuan Journal: Atherosclerosis Date: 2017-01-12 Impact factor: 5.162
Authors: Hilla-Lee Veiner; Rostic Gorbatov; Moshe Vardi; Gheorghe Doros; Rachel Miller-Lotan; Yaniv Zohar; Edmond Sabo; Rabea Asleh; Nina S Levy; Levi J Goldfarb; Thomas A Berk; Tali Haas; Hadar Shalom; Edith Suss-Toby; Adi Kam; Marielle Kaplan; Ronit Tamir; Anna Ziskind; Andrew P Levy Journal: Atherosclerosis Date: 2015-01-14 Impact factor: 5.162
Authors: Rabea Asleh; Farid M Nakhoul; Rachel Miller-Lotan; Hoda Awad; Dan Farbstein; Nina S Levy; Nakhoul Nakhoul; Theodore C Iancu; Irena Manov; Michael Laue; Maret G Traber; Katie M Lebold; Andrew P Levy Journal: Free Radic Biol Med Date: 2012-06-27 Impact factor: 7.376