Serum apolipoprotein C‐III in high‐density lipoprotein: a key diabetogenic risk factor in Turks

Onat, Altan; Hergenç, Gülay; Ayhan, Erkan; Uğur, Murat; Kaya, Hasan; Tuncer, Mustafa; Can, Günay

doi:10.1111/j.1464-5491.2009.02814.x

Cited by 54 publications

(44 citation statements)

References 29 publications

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“…In addition, the development of MetS and diabetes was predicted by apoA-II concentrations, irrespective of HDL-cholesterol concentrations. This phenomenon is consistent with previously demonstrated cardiometabolic risk conferred by similar functional alterations in HDL (17), apoA-I (15), apoC-III in HDL (18) and in adiponectin (29) in the TARF cohort.…”

Section: Manifestations Of Impaired Anti-inflammatory/ Anti-oxidativesupporting

confidence: 80%

“…However, recent prospective analyses in the TARF showed that increased serum apo A-I was diabetogenic and tended to be atherogenic among Turks (15). In addition, increased concentrations of adiponectin (16), HDL-cholesterol (17) and apoC-III in HDL (18) showed similar effects. The abnormal func-tions of these normally protective serum proteins have been proposed to result from an environment of atherogenic dyslipidemia, excessive oxidative stress and systemic low-grade inflammation associated with the high prevalence of MetS among Turks (19).…”

Section: Introductionmentioning

confidence: 71%

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Impaired anti-inflammatory function of apolipoprotein A-II concentrations predicts metabolic syndrome and diabetes at 4 years follow-up in elderly Turks

Onat¹,

Hergenç²,

Ayhan³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: We evaluated prospectively the predictive value of serum apolipoprotein (apo) A-II, the second major apolipoprotein of high-density lipoprotein (HDL), for cardiometabolic risk in Turkish adults showing abnormalities in other proteins that normally confer protection. Methods: Determinants of apoA-II and its associations with coronary heart disease (CHD), metabolic syndrome (MetS) and diabetes were investigated at 4 years follow-up in 193 elderly men and women. Results: ApoA-II concentrations at baseline, in addition to being significantly related to HDL-cholesterol, were directly associated with complement C3 in multivariate linear regression analyses comprising nine variables. Following adjustment for gender, age and HDL-cholesterol ()30/)33 g/L, in men and women, respectively), low serum apoA-II concentrations predicted incident MetS wrelative risk (RR) 3.5 (95% CI 1.4; 8.6)x and type 2 diabetes wRR 4.5 (95% CI 1.3; 15.6)x in both genders at an increment of 1 SD. Increased apoA-II values were not associated with prevalent or incident CHD, and tended to be marginally atheroprotective only in males. Conclusions: Serum apoA-II concentrations confer risk for MetS and diabetes and exhibit evidence of anti-inflammatory properties among Turks. These findings support the effects seen for several other HDL protein constituents. This finding may explain the increased cardiometabolic risk among Turks. Clin Chem Lab Med 2009;47:1389-94.

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Section: Manifestations Of Impaired Anti-inflammatory/ Anti-oxidativesupporting

confidence: 80%

Section: Introductionmentioning

confidence: 71%

Impaired anti-inflammatory function of apolipoprotein A-II concentrations predicts metabolic syndrome and diabetes at 4 years follow-up in elderly Turks

Onat¹,

Hergenç²,

Ayhan³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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“…We studied the distribution of these different apolipoproteindefi ned HDL types in a group with normal HDL-C levels and normal body weight and compared it with that of an obese group, a common high-risk phenotype associated with low HDL-C. Elevated apoC-III concentrations in HDL ( 34,35 ), as well as increased apoC-III production ( 36 ), are common features of obesity. We hypothesized that the distribution of HDL particles is disturbed with obesity, such that obese subjects have higher concentrations of HDL with apoC-III as well as HDL with apoE, and lower concentrations of HDL without apoE or apoC-III contributing to their increased risk for CHD.…”

Section: Isolation Of Hdl From Plasma By Immunoaffi Nity Chromatographymentioning

confidence: 99%

Obesity favors apolipoprotein E- and C-III-containing high density lipoprotein subfractions associated with risk of heart disease

Talayero

Wang

Furtado

et al. 2014

Journal of Lipid Research

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with an elevated risk of coronary heart disease (CHD) ( 1-5 ). However, evidence from randomized clinical trials that studied drugs that increased HDL-C has not been consistent with the hypothesis that HDL protects against CHD. In large-scale trials of novel cholesteryl ester transfer protein inhibitors, CHD incidence was not reduced despite substantial increases in HDL-C levels ( 6-8 ); trials of estrogen replacement therapy in postmenopausal women did not confi rm a protective effect on CHD despite increases in HDL-C ( 9-11 ); and two recent trials of niacin also failed to show reduction in CHD risk, although the increases in HDL-C were modest ( 12, 13 ). Furthermore, some genetic variation that is associated with high HDL-C concentration is not associated with reduced CHD ( 14 ). This raises questions regarding the effi cacy of HDL-C elevation, in general, as a strategy for CHD prevention.Accumulating evidence indicates that protein composition of HDL may be relevant to the risk of CHD ( 15-17 ). ApoE and apoC-III are found on the surface of both triglyceride-rich lipoproteins (TRLs) and . The concentration of apoE in HDL is an independent predictor of recurrent coronary events ( 15 ). More recently, a proteomic analysis showed greater apoE enrichment in small-size HDL (HDL3) in subjects with established coronary artery disease than in normal controls ( 16 ). Similarly, HDL containing apoC-III independently predicts increased risk of an initial coronary event in separate cohorts of men and women ( 17 ), and a high ratio of apoC-III to apoA-I in HDL predicts recurrent coronary events ( 15 ).Abstract Human HDLs have highly heterogeneous composition. Plasma concentrations of HDL with apoC-III and of apoE in HDL predict higher incidence of coronary heart disease (CHD). The concentrations of HDL-apoA-I containing apoE, apoC-III, or both and their distribution across HDL sizes are unknown. We studied 20 normal weight and 20 obese subjects matched by age, gender, and race. Plasma HDL was separated by sequential immunoaffi nity chromatography (anti-apoA-I, anti-apoC-III, anti-apoE), followed by nondenaturing-gel electrophoresis. Mean HDL-cholesterol concentrations in normal weight and obese subjects were 65 and 50 mg/dl ( P = 0.009), and total apoA-I concentrations were 119 and 118 mg/dl, respectively. HDL without apoE or apoC-III was the most prevalent HDL type representing 89% of apoA-I concentration in normal weight and 77% in obese ( P = 0.01) individuals; HDL with apoE-only was 5% versus 8% ( P = 0.1); HDL with apoC-III-only was 4% versus 10% ( P = 0.009); and HDL with apoE and apoC-III was 1.5% versus 4.6% ( P = 0.004). Concentrations of apoE and apoC-III in HDL were 1.5-2× higher in obese subjects ( P р 0.004). HDL with apoE or apoC-III occurred in all sizes among groups. Obese subjects had higher prevalence of HDL containing apoE or apoC-III, subfractions associated with CHD, whereas normal weight subjects had higher prevalence of HDL without apoE or apoC-III, subfractions with protective association against ...

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“…Total and LDL-cholesterol tended to be lower in the CHD group and LDL-cholesterol tended to be inversely associated with CHD, while apoB levels were significantly and positively associated with CHD likelihood. These findings suggest that HDL-apoCIII may assume atherogenic properties (just as it was shown in 2008 by us [10] to assume diabetogenic properties) in an environment of low LDLcholesterol (and high apoB), consistent with autoimmune involvement of Lp(a) protein, but not of apoB. Moreover, of interest is the finding of…”

Section: Individual Plasma Proteins Epidemiologically Identified As Hmentioning

confidence: 64%

Underlying Autoimmune Activation Rendering Paradoxical Non-Linear Relationship between Biomarkers and Cardiometabolic Risk

Onat¹,

Kaya²

2016

J Clin Cell Immunol

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Serum apolipoprotein C‐III in high‐density lipoprotein: a key diabetogenic risk factor in Turks

Cited by 54 publications

References 29 publications

Impaired anti-inflammatory function of apolipoprotein A-II concentrations predicts metabolic syndrome and diabetes at 4 years follow-up in elderly Turks

Impaired anti-inflammatory function of apolipoprotein A-II concentrations predicts metabolic syndrome and diabetes at 4 years follow-up in elderly Turks

Obesity favors apolipoprotein E- and C-III-containing high density lipoprotein subfractions associated with risk of heart disease

Underlying Autoimmune Activation Rendering Paradoxical Non-Linear Relationship between Biomarkers and Cardiometabolic Risk

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