Assignment of the Binding Site for Haptoglobin on Apolipoprotein A-I

Spagnuolo, Maria Stefania; Cigliano, Luisa; D’Andrea, Luca Domenico; Pedone, Carlo; Abrescia, Paolo

doi:10.1074/jbc.m411390200

Cited by 76 publications

(94 citation statements)

References 58 publications

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“…Hp is an HDL-associated protein in humans. Hp has been shown by some but not all investigators to be an HDL-associated protein (24,(27)(28)(29). Critical analysis of these prior studies suggested that the key difference in these studies was in the manner in which the HDL was prepared.…”

Section: Resultsmentioning

confidence: 99%

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Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype

et al. 2008

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OBJECTIVE-Pharmacogenomics is a key component of personalized medicine. The Israel Cardiovascular Events Reduction with Vitamin E Study, a prospective placebo-controlled study, recently demonstrated that vitamin E could dramatically reduce CVD in individuals with diabetes and the haptoglobin (Hp) 2-2 genotype (40% of diabetic individuals). However, because of the large number of clinical trials that failed to demonstrate benefit from vitamin E coupled with the lack of a mechanistic explanation for why vitamin E should be beneficial only in diabetic individuals with the Hp 2-2 genotype, enthusiasm for this pharmacogenomic paradigm has been limited. In this study, we sought to provide such a mechanistic explanation based on the hypothesis that the Hp 2-2 genotype and diabetes interact to promote HDL oxidative modification and dysfunction.RESEARCH DESIGN AND METHODS-Hb and lipid peroxides were assessed in HDL isolated from diabetic individuals or mice with the Hp 1-1 or Hp 2-2 genotypes. HDL function was assessed based on its ability to promote cholesterol efflux from macrophages. A crossover placebo-controlled study in Hp 2-2 diabetic humans and in Hp 1-1 and Hp 2-2 diabetic mice assessed the ability of vitamin E to favorably modify these structural and functional parameters.RESULTS-Hb and lipid peroxides associated with HDL were increased and HDL function was impaired in Hp 2-2 diabetic individuals and mice. Vitamin E decreased oxidative modification of HDL and improved HDL function in Hp 2-2 diabetes but had no effect in Hp 1-1 diabetes.CONCLUSIONS-Vitamin E significantly improves the quality of HDL in Hp 2-2 diabetic individuals.

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Section: Resultsmentioning

confidence: 99%

“…A binding site for Hp on ApoA1 (amino acid residues 141-164) has been identified (27). Interestingly, lecithin acyl transferase (LCAT), whose activity is dependent on its binding to ApoA1, binds to ApoA1 residues 159 -170 (34).…”

Section: Discussionmentioning

confidence: 99%

Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype

et al. 2008

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“…In humans, Hp is synthesized by adipocytes as well as by hepatocytes, 9 and Hp locus is close to the loci of lipid-related enzymes such as lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein. 20 Moreover, Hp is attached to high-density lipoproteins (HDL) and apolipoproteins (apo) such as apoA-I 24 and apoE 4 in humans, and to HDL and very high-density lipoproteins in cows. 12 Significant increases in Hp appeared in fasted goats at the same time as the clinical signs in the present study.…”

Section: Discussionmentioning

confidence: 99%

Acute Phase Proteins in Experimentally Induced Pregnancy Toxemia in Goats

et al. 2011

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Abstract. The present work aimed to study the behavior of acute phase proteins (haptoglobin, serum amyloid A, acid soluble glycoprotein, fibrinogen, and albumin) in fasting-induced pregnancy toxemia in goats and their relationship with classical indicators of this disorder such as beta-hydroxybutyrate and nonesterified fatty acids in the blood and decreased urine pH and ketonuria. Twelve adult Murciano-Granadina goats at the final stage of gestation were used in this experiment. Pregnancy toxemia was induced in 6 goats by fasting for 72 hr. The other 6 animals were used as control group. Ketonuria was present in 4 out of 5 fasting animals at 24 hr and in all fasting animals at 48 hr of fasting. Serum nonesterified fatty acids were significantly increased at 24, 48, and 72 hr of fasting. Beta-hydroxybutyrate and haptoglobin achieved significantly increased concentrations at 48 hr and 72 hr, respectively, remaining increased during the entire study. Serum amyloid A, acid soluble glycoprotein, fibrinogen, and albumin were not affected by fasting. In conclusion, acute phase proteins (including haptoglobin) seemed not to have an advantage over traditional markers in diagnosis of fasting-induced pregnancy toxemia in goats.

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“…106 This has been attributed to elevated levels of haptoglobin in these individuals that bind to apoA-I and reduce its availability for the LCAT reaction. 107 LCAT activity is also decreased in chronic renal disease, 108 possibly as a consequence of reduced transcription of the LCAT gene in the liver.…”

Section: Regulation Of Spherical Hdl Biogenesis In Disease Statesmentioning

confidence: 99%

Regulation of High-Density Lipoprotein Metabolism

Rye

Barter

2014

Circulation Research

100

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There is compelling evidence from human population studies that plasma levels of high-density lipoprotein (HDL) cholesterol correlate inversely with cardiovascular risk. Identification of this relationship has stimulated research designed to understand how HDL metabolism is regulated. The ultimate goal of these studies has been to develop HDL-raising therapies that have the potential to decrease the morbidity and mortality associated with atherosclerotic cardiovascular disease. However, the situation has turned out to be much more complex than originally envisaged. This is partly because the HDL fraction consists of multiple subpopulations of particles that vary in terms of shape, size, composition, and surface charge, as well as in their potential cardioprotective properties. This heterogeneity is a consequence of the continual remodeling and interconversion of HDL subpopulations by multiple plasma factors. Evidence that the remodeling of HDLs may impact on their cardioprotective properties is beginning to emerge. This serves to highlight the importance of understanding not only how the remodeling and interconversion of HDL subpopulations is regulated but also how these processes are affected by agents that increase HDL levels. This review provides an overview of what is currently understood about HDL metabolism and how the subpopulation distribution of these lipoproteins is regulated.

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Assignment of the Binding Site for Haptoglobin on Apolipoprotein A-I

Cited by 76 publications

References 58 publications

Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype

Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype

Acute Phase Proteins in Experimentally Induced Pregnancy Toxemia in Goats

Regulation of High-Density Lipoprotein Metabolism

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