Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis

Kontush, Anatol; Chapman, M. John

doi:10.1124/pr.58.3.1

Cited by 654 publications

(656 citation statements)

References 467 publications

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“…Serum levels of SAA rise with obesity, diabetes and the metabolic syndrome 10,11. Some studies point to a positive correlation between SAA and angiographically proven coronary artery disease, and serum concentration of SAA is reported to be a powerful predictor of cardiovascular events 12,13. It has been shown that patients with a high SAA concentration have more active atherosclerotic disease,14 but the relationship between serum SAA levels and transient myocardial ischaemia during exercise is not known.…”

Section: Discussionmentioning

confidence: 99%

Serum high-sensitivity C-reactive protein, amyloid-associated protein and N-terminal proBNP levels do not predict reversible myocardial ischaemia

Başkurt¹,

Aktürk²,

Keskin³

et al. 2011

CardioVascular Journal of Africa

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AimThe aim of this study was to detect any relationship between serum high-sensitivity C-reactive protein (hs-CRP), serum amyloid-associated protein (SAA) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and reversible myocardial ischaemia during cardiovascular exercise tests and to determine whether these biomarkers could predict transient myocardial ischaemia.MethodsNinety-six patients (36 women, 60 men, mean age 57 ± 8.5 years) were included in the study. Venous blood samples were taken from patients before and 15 minutes after exercise testing. SAA and hs-CRP were analysed using immunonephelometric assays (Dade-Behring, BN II, Marburg, Germany). NT-proBNP (pg/ml) was determined using the immulite 1 000 chemiluminescence immunoassay system (Siemens Medical Solution Diagnostics, Deerfiled, USA). Forty-eight patients (18 women, 30 men) with positive exercise tests were allocated to the exercise-positive group and 48 (18 women, 30 men) with negative exercise tests were put in the exercise-negative group. Coronary angiography was performed on all patients in the exercise-positive group.ResultsThere was no difference between the levels of hs-CRP, SAA and NT-pro-BNP before and after exercise testing in both of the exercise groups.ConclusionSerum levels of hs-CRP, SAA and NT-proBNP could not predict the occurrence of reversible myocardial ischaemia during exercise. Large-scale clinical studies are needed to clarify the status of hs-CRP, SAA and NT-proBNP with exercise.

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Section: Discussionmentioning

confidence: 99%

Serum high-sensitivity C-reactive protein, amyloid-associated protein and N-terminal proBNP levels do not predict reversible myocardial ischaemia

Başkurt¹,

Aktürk²,

Keskin³

et al. 2011

CardioVascular Journal of Africa

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“…In these situations, the lipid and protein composition of HDLs can be changed via oxidative processes. As a result, the protective effect of HDLs against CHD was lost and HDLs became proatherogenic, which are known as dysfunctional HDLs (16,17,18). Ansell et al (19) showed that HDLs from subjects with CHD were proinflammatory despite very high HDL-C levels, indicating that HDLs from CHD subjects are dysfunctional.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

“…One possible mechanism for dysfunctional HDLs is the alteration in the protein composition of HDLs in the setting of systemic inflammation and T2D. In this situation, inflammatory cytokines such as plasma interleukin-6 levels are elevated and the liver consequently produces serum amyloid A, which replaces apoA-I and paraoxonase 1 in HDL particles (16). In addition, myeloperoxidase specifically binds to apoA-I and produces reactive oxidative species.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Association of HDL-C and apolipoprotein A-I with the risk of type 2 diabetes in subjects with impaired fasting glucose

Hwang

Ahn

Park

et al. 2014

European Journal of Endocrinology

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Objectives: HDLs have many diverse functions. The goal of this study was to determine the association of HDL cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) with the development of type 2 diabetes (T2D). In particular, this study determined the association between the ratio of HDL-C to apoA-I (HA) and incident T2D. Design and methods: A total of 27 988 subjects with impaired fasting glucose (IFG) (18 266 men and 9722 women) aged 21-91 years (mean age 40.7 years) were followed for a mean duration of 2.81 years. Results: Study subjects were divided into quartiles according to the baseline HA ratio. Age, male sex, current smoking, BMI, waist circumference, and high-sensitivity C-reactive protein decreased across the quartiles, and all metabolic profiles, including blood pressure, fasting glucose, insulin resistance as determined by homeostasis model assessment of insulin resistance, and lipid measurements such as total cholesterol, LDL cholesterol, non-HDL-C, and apoB, improved as the HA ratio increased. In addition, incident cases of T2D decreased as the HA ratio increased, independent of age, sex, BMI, current smoking, systolic blood pressure, HbA1c, fasting serum insulin, family history of diabetes, and serum triglyceride concentrations (HR (95% CI) of fourth quartile vs first quartile; 0.76 (0.67-0.86), P!0.0001). Conclusions: A higher HA ratio was associated with favorable metabolic profiles and a lower risk of T2D development in subjects with IFG.

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“…Thus, cell cholesterol efflux to HDL, a key early step in reverse cholesterol transport mediated by ATP-binding cassette transporter A1, is reportedly impaired upon HDL oxidation. [14][15][16][17][18][19] This impairment has been ascribed to specific protein modifications such as oxidation of two-to-three Met in the major HDL protein, apolipoprotein A-I (apoA-I), that occurs at initial stages of HDL oxidation, 20-22 along with tyrosylation and protein cross-linking via the modified Tyr or Lys. 13,16,17,23 However, several studies report that oxidation enhances rather than impairs HDL functions in stimulating lipid efflux from cells 22,24-26 and protecting against atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Mild Oxidation Promotes and Advanced Oxidation Impairs Remodeling of Human High-Density Lipoprotein In Vitro

Gao

Jayaraman

Gursky

2008

Journal of Molecular Biology

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SUMMARYHigh-density lipoproteins (HDL) prevent atherosclerosis by removing cholesterol from macrophages and by exerting anti-oxidant and anti-inflammatory effects. Oxidation is thought to impair HDL functions, yet certain oxidative modifications may be advantageous; thus, mild oxidation reportedly enhances cell cholesterol uptake by HDL whereas extensive oxidation impairs it. To elucidate the underlying energetic and structural basis, we analyzed the effects of copper and hypochlorite (that preferentially oxidize lipids and proteins, respectively) on thermal stability of plasma spherical HDL. Circular dichroism, light scattering, calorimetry, gel electrophoresis and electron microscopy showed that mild oxidation destabilizes HDL and accelerates protein dissociation and lipoprotein fusion, while extensive oxidation inhibits these reactions; this inhibition correlates with massive protein cross-linking and lipolysis. We propose that mild oxidation lowers kinetic barriers for HDL remodeling due to diminished apolipoprotein affinity for lipids resulting from oxidation of methionine and aromatic residues in apolipoproteins A-I and A-II followed by protein cross-linking into dimers and/or trimers. In contrast, advanced oxidation inhibits protein dissociation and HDL fusion due to lipid re-distribution from core to surface upon lipolysis and to massive protein crosslinking. Our results help reconcile the apparent controversy in the studies of oxidized HDL and suggest that mild oxidation may benefit HDL functions.

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Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis

Cited by 654 publications

References 467 publications

Serum high-sensitivity C-reactive protein, amyloid-associated protein and N-terminal proBNP levels do not predict reversible myocardial ischaemia

Serum high-sensitivity C-reactive protein, amyloid-associated protein and N-terminal proBNP levels do not predict reversible myocardial ischaemia

Association of HDL-C and apolipoprotein A-I with the risk of type 2 diabetes in subjects with impaired fasting glucose

Mild Oxidation Promotes and Advanced Oxidation Impairs Remodeling of Human High-Density Lipoprotein In Vitro

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