Haptoglobin phenotype as a predictor of restenosis after percutaneous transluminal coronary angioplasty

Roguin, Ariel; Hochberg, Irit; Nikolsky, Eugenia; Markiewicz, Walter; Meisel, Simcha; Hir, Jamal; Grenadier, Ehud; Beyar, Rafael; Levy, Andrew P.

doi:10.1016/s0002-9149(00)01368-0

Cited by 45 publications

(34 citation statements)

References 15 publications

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“…The increased antioxidant function of Hp1 is thought to confer protection from angiopathies. This has been reported for coronary (10) and peripheral (11) atherosclerotic lesions, cardiac transplant vasculopathy (12), diabetic nephropathy (13), mortality in coronary heart disease (14), restenosis after peripheral and coronary angioplasty (15) or stenting (16), and cardiovascular disease in diabetic individuals (17). The overall picture appears to confirm a protective role of Hp1 in clinical settings associated with increased oxidative stress.…”

supporting

confidence: 54%

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Haptoglobin Phenotype and Gestational Diabetes

et al. 2004

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OBJECTIVE -Haptoglobin (Hp), an Hb-binding plasma protein, exists in two major allelic variants. Hp1 has higher Hb binding and antioxidant capacity compared with Hp2. Individuals with Hp1 exhibit a lower incidence of angiopathies. Gestational diabetes mellitus (GDM) is an early manifestation of type 2 diabetes in pregnant women. It is usually confined to the time of gestation, but carries an increased risk to develop type 2 diabetes later in life.RESEARCH DESIGN AND METHODS -From consecutive Caucasian pregnant women (n ϭ 250) referred for oral glucose tolerance testing, the Hp phenotype was determined. Significance of distribution and odds ratios (ORs) associated with Hp phenotype were calculated for women with GDM (n ϭ 110) and women with normal glucose tolerance (n ϭ 140).RESULTS -Frequency of GDM in Hp phenotype classes increased with the number of Hp2 alleles (P Ͻ 0.001). ORs for GDM in women heterozygous and homozygous for Hp2 were 2.7 (95% CI 1.06 -6.84) and 4.2 (1.67-10.55), respectively. CONCLUSIONS -Hp phenotype is an apparent risk factor for the development of GDM in our study population. This might be due to the low antioxidative potential of Hp2 compared with Hp1. Diabetes Care 27:2103-2107, 2004H aptoglobin (Hp) is an acute-phase protein synthesized in the liver and, to some extent, in fat tissue (1) in response to interleukin 6 -type cytokines. The Hp gene is located on the long arm of chromosome 16 (16q22.3) (2). The two major Hp alleles (Hp1 and Hp2) are coding for proteins with one (Hp1) or two (Hp2) SH groups used in multimerization. The Hp1 molecule forms only dimers with a molecular weight of 86 kDa, whereas the Hp2 molecule forms multimers with a molecular weight between 170 and 900 kDa. A mixture of Hp1 and Hp2, as present in heterozygous individuals, exhibits dimeric Hp as well as oligomeric Hp, but the latter with a lower degree of polymerization than in Hp2 homozygotes. The Hp phenotype is inherited in a Mendelian pattern.Hp forms complexes with free Hb that are rapidly cleared by the liver and by macrophages. Rapid complexation of free Hb, stemming from common, low-grade intravascular hemolysis (3), is important because free Hb catalyzes the generation of reactive oxygen species, like the extremely reactive hydroxyl radical, by the so-called Fenton reaction. Reactive oxygen species promote endothelial activation and inflammation and play a crucial role in the development of endothelial dysfunction (4), which is also observed in gestational diabetes mellitus (GDM) (5). Thus Hp functions as an antioxidant and an essential vascular endothelial protector. However, the Hb-binding capacity (6) and antioxidant capacity of Hp1 is higher compared with Hp2 (7-9). The increased antioxidant function of Hp1 is thought to confer protection from angiopathies. This has been reported for coronary (10) and peripheral (11) atherosclerotic lesions, cardiac transplant vasculopathy (12), diabetic nephropathy (13), mortality in coronary heart disease (14), restenosis after peripheral and coronary angioplasty ...

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supporting

confidence: 54%

“…GDM is a most common complication of pregnancy and carries considerable health risks for both the fetus and the mother (15). It is well established that glucose intolerance detected during pregnancy is predictive of later maternal type 2 diabetes (18,19).…”

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confidence: 99%

Haptoglobin Phenotype and Gestational Diabetes

et al. 2004

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“…The Belgian Interuniversity Research on Nutrition and Health Study found the overall death rate from myocardial infarction to be reduced in patients carrying the 2-2 haptoglobin genotype (9). In patients expressing haptoglobin 2-2, coronary bypass graft survival time is reduced because of increased intimal hyperplasia (12,35). One study suggested that a haptoglobin 1 allele in diabetic patients improves coronary collateralization; however, this is likely to be an indirect effect of the improved antioxidant function of the 1-1 allele (16,20).…”

Section: Discussionmentioning

confidence: 99%

Haptoglobin expression and activity during coronary collateralization

Lohr

Warltier²,

Chilian³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Coronary collateral development relies on the coordinated secretion of growth factors. However, alone they are insufficient for permanent collateral growth. We utilized proteomics to identify other important proteins in the extracellular environment that could facilitate collateralization. Chronically instrumented dogs developed coronary collaterals by the repetitive occlusion method. Subendocardial (0.19 Ϯ 0.04, 0.27 Ϯ 0.06, 0.48 Ϯ 0.10, and 0.81 Ϯ 0.11 ml ⅐ min Ϫ1 ⅐ g Ϫ1 on days 1, 7, 14, and 21, respectively) and subepicardial (0.14 Ϯ 0.01, 0.36 Ϯ 0.06, 0.51 Ϯ 0.07, and 0.71 Ϯ 0.08 ml ⅐ min Ϫ1 ⅐ g Ϫ1 on days 1, 7, 14, and 21, respectively) blood flow increased in animals subjected to repetitive occlusion. Sham animals exhibited no changes in blood flow. Myocardial interstitial fluid (MIF) from both groups was analyzed by two-dimensional electrophoresis with matrix-assisted laser desorption/ionization time-of-flight identification. The acute-phase protein haptoglobin was identified in the group subjected to repetitive occlusion. ELISA of MIF showed haptoglobin to be elevated at all time points of collateral development compared with sham, with maximal production on day 7. Purified haptoglobin dose dependently stimulated endothelial cells to form tubes and vascular smooth muscle cells to migrate. Purified haptoglobin did not stimulate proliferation of either cell type. The relative contribution of haptoglobin to the chemotactic properties of MIF was tested using a neutralizing antibody. Neutralized MIF could not stimulate smooth muscle cells to migrate at any time during collateral development. Endothelial cell tube formation was inhibited after the midpoint of collateralization. Therefore, the acute-phase protein haptoglobin plays a critical role during coronary collateralization.angiogenesis; coronary circulation; inflammation; proteins CORONARY ARTERY DISEASE is characterized by plaque deposition, which ultimately reduces blood flow and leads to the pathophysiological sequelae of ischemic heart disease. Clinical data demonstrate that development of the coronary collateral circulation can ameliorate complications of coronary disease. Perez-Castellano et al. (33) associated reduced patient mortality from myocardial infarction with the extent of collateral development. Coronary collaterals can also reduce infarct size, preserve myocardial architecture, and improve cardiac function (5, 19).Coronary collaterals are preexisting arterial anastomoses between coronary arteries. These vessels cannot conduct blood flow sufficient to prevent ischemia in the event of coronary occlusion because of their small caliber and high resistance in their native state (10). However, collaterals can dramatically increase in diameter and muscularity when stimulated (10). Vascular endothelial growth factor (VEGF) has been identified as important in collateralization, and administration of VEGF or transfection in vivo enhances angiogenesis and collateral growth in many models (4,23,24,26). Basic fibroblast growth factor (bFGF), a mitog...

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“…Jormsjö et al (20 ) recently described two common polymorphisms in the promoter region of the MMP7 gene that are functional in vitro and seem to influence coronary artery dimensions. Both polymorphisms influenced the binding of nuclear proteins.…”

Section: Colorectal Carcinoma Susceptibility and Metastasesmentioning

confidence: 99%

“…Of particular interest is the question whether the repeatedly demonstrated clinical relevance of the haptoglobin polymorphism (1,2,(17)(18)(19)(20)(21) is associated with a specific subtype. Tumor invasion and metastasis are important aspects of tumor progression, and the formation of tumor metastasis is a principal contributing factor to cancer morbidity and mortality (1 ).…”

mentioning

confidence: 99%