Haptoglobin Genotype-dependent Differences in Macrophage Lysosomal Oxidative Injury

Asleh, Rabea; Ward, John A.; Levy, Nina S.; Safuri, Shady; Aronson, Doron; Levy, Andrew P.

doi:10.1074/jbc.m114.554212

Cited by 13 publications

(12 citation statements)

References 59 publications

(65 reference statements)

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“…Moreover, Hp, as one kind of acute phase protein, plays an important role in the process of host anti-infection, the repairing of tissue and stabilizing internal environment, the content of serum Hp has a significant rise in pathological conditions such as infection, trauma, inflammation, tumor and myocardial infarction (MI). In addition to the above functions, Hp has also involved in oxidative stress, immune response, and so on (Asleh et al, 2014;Bertaggia et al, 2014;Tan et al, 2014). This study found that Hp level significantly increased in the lung cancer patients group.…”

Section: Discussionsupporting

confidence: 48%

Clinical Utility of Haptoglobin in Combination with CEA, NSE and CYFRA21-1 for Diagnosis of Lung Cancer

Wang¹,

He²,

Tian³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Discussionsupporting

confidence: 48%

Clinical Utility of Haptoglobin in Combination with CEA, NSE and CYFRA21-1 for Diagnosis of Lung Cancer

Wang¹,

He²,

Tian³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…The Hp-Hb complex binds with high affinity to the monocyte/macrophage CD163 receptor allowing clearance of Hb from the plasma or the vessel wall. Clearance of the Hp 2-2-Hb complex by CD163 [38] mediated receptor mediated endocytosis [22,28] and processing of the Hp 2-2-Hb complex within the lysosome is impaired leading to accumulation of iron in the lysosome and lysosomal injury [39]. Furthermore, the binding of Hp 1-1-Hb to CD163 results in the release of anti-inflammatory cytokines (i.e.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability

Viener¹,

Gorbatov²,

Vardi³

et al. 2015

Atherosclerosis

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Structured Abstract Objective Homozygosity for a 1.7kb intragenic duplication of the Haptoglobin (Hp) gene (Hp 2-2 genotype), present in 36% of the population, has been associated with a 2–3 fold increased incidence of atherothrombosis in individuals with Diabetes (DM) in 10 longitudinal studies compared to DM individuals not homozygous for this duplication (Hp 1-1/2-1). The increased CVD risk associated with the Hp 2-2 genotype has been shown to be prevented with vitamin E supplementation in man. We sought to determine if there was an interaction between the Hp genotype and vitamin E on atherosclerotic plaque growth and stability in a transgenic model of the Hp polymorphism. Methods and Results Brachiocephalic artery atherosclerotic plaque volume was serially assessed by high resolution ultrasound in 28 Hp 1-1 and 26 Hp 2-2 mice in a C57Bl/6 ApoE−/− background. Hp 2-2 mice had more rapid plaque growth and an increased incidence of plaque hemorrhage and rupture. Vitamin E significantly reduced plaque growth in Hp 2-2 but not in Hp 1-1 mice with a significant pharmacogenomic interaction between the Hp genotype and vitamin E on plaque growth. Conclusions These results may help explain why vitamin E supplementation in man can prevent CVD in Hp 2-2 DM but not in non Hp 2-2 DM individuals.

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“…We have not quantified lipid peroxidation or other markers of oxidation in our study patients, nor have we measured catalytic iron levels. Nonetheless, others have already reported that diabetic patients with the Hp 2-2 phenotype have increased oxidative stress 56 and increased levels of catalytic iron, 57,58 and an association between excessive oxidation and AKI after cardiac surgery has been reported. 24 Second, we assumed that the elevated cell-free hemoglobin and the blunted decrease in haptoglobin in the Hp 2-2 group are the results of decreased Hp/Hb complex formation and decreased binding of the Hp 2-2/Hb complex to the CD163 receptor in the context of CPB-induced hemolysis; however, these findings may also occur as a result of decreased expression of the CD163 receptor.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Haptoglobin 2‐2 Phenotype Is Associated With Increased Acute Kidney Injury After Elective Cardiac Surgery in Patients With Diabetes Mellitus

Feng

Naik

Xin

et al. 2017

JAHA

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BackgroundRecent studies reported an association between the 2‐2 phenotype of haptoglobin (Hp 2‐2) and increased cardiorenal morbidity in nonsurgical diabetic patients. Our goal was to determine whether the Hp 2‐2 phenotype was associated with acute kidney injury (AKI) after elective cardiac surgery in patients with diabetes mellitus.Methods and ResultsWe prospectively enrolled 99 diabetic patients requiring elective cardiac surgery with cardiopulmonary bypass. Haptoglobin phenotypes were determined by gel electrophoresis. Cell‐free hemoglobin, haptoglobin, and total serum bilirubin were quantified as hemolysis markers. The primary outcome was postoperative AKI, as defined by the Acute Kidney Injury Network classification. The incidence of AKI was significantly higher in Hp 2‐2 patients compared with patients without this phenotype (non–Hp–2‐2; 55.6% versus 27%, P<0.01). The need for renal replacement therapy was also significantly higher in the Hp 2‐2 group (5 patients versus 1 patient, P=0.02). Thirty‐day mortality (3 versus 0 patients, P=0.04) and 1‐year mortality (5 versus 0 patients, P<0.01) were also significantly higher in patients with the Hp 2‐2 phenotype. In multivariable analysis, Hp 2‐2 was an independent predictor of postoperative AKI (P=0.01; odds ratio: 4.17; 95% confidence interval, 1.35–12.48).ConclusionsHp 2‐2 phenotype is an independent predictor of postoperative AKI and is associated with decreased short and long‐term survival after cardiac surgery in patients with diabetes mellitus.

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Haptoglobin Genotype-dependent Differences in Macrophage Lysosomal Oxidative Injury

Cited by 13 publications

References 59 publications

Clinical Utility of Haptoglobin in Combination with CEA, NSE and CYFRA21-1 for Diagnosis of Lung Cancer

Clinical Utility of Haptoglobin in Combination with CEA, NSE and CYFRA21-1 for Diagnosis of Lung Cancer

Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability

Haptoglobin 2‐2 Phenotype Is Associated With Increased Acute Kidney Injury After Elective Cardiac Surgery in Patients With Diabetes Mellitus

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