Serum IF1 concentration is independently associated to HDL levels and to coronary heart disease: the GENES study

Genoux, Annelise; Ruidavets, Jean‐Bernard; Ferrières, Jean; Combes, Guillaume; Lichtenstein, Laeticia; Pons, Véronique; Laffargue, Muriel; Carrié, Didier; Elbaz, Meyer; Fougère, Bertrand; Martinez, Laurent O.

doi:10.1194/jlr.p036335

Cited by 31 publications

(46 citation statements)

References 39 publications

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“…Adenylate kinase and niacin are important factors that regulate HDL metabolism and plasma levels via ecto-F1-ATPase (Fabre et al 2006;Zhang et al 2008). Inhibitors of ecto-F1-ATPase or adenylate kinase activity that consume ADP generated by ecto-F1-ATPase downregulate holo-HDL particle uptake (Genoux et al 2013). In vivo studies using a P2Y 13 -deficient mouse model also indicated that the P2Y 13 ADP receptor may have an important role in HDL-mediated reverse cholesterol transport (Fabre et al 2010).…”

Section: 7mentioning

confidence: 97%

“…The ecto-F 1 -ATPase protein, which resides on cell membranes, hydrolyzes ATP to ADP and phosphate and can be inhibited by the mitochondrial inhibitor protein IF 1 . It was recently shown that IF1 is present in the serum, and its concentration correlates negatively with HDL-C levels and the risk for coronary heart disease (Genoux et al 2013). Binding of lipid-free apoA-I to the high affinity side of ecto-F 1 -ATPase enhances binding of HDL to the low-affinity binding sites.…”

Section: 7mentioning

confidence: 98%

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HDL Biogenesis, Remodeling, and Catabolism

Zannis

Fotakis

Κούκος

et al. 2014

Handbook of Experimental Pharmacology

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In this chapter, we review how HDL is generated, remodeled, and catabolized in plasma. We describe key features of the proteins that participate in these processes, emphasizing how mutations in apolipoprotein A-I (apoA-I) and the other proteins affect HDL metabolism. The biogenesis of HDL initially requires functional interaction of apoA-I with the ATP-binding cassette transporter A1 (ABCA1) and subsequently interactions of the lipidated apoA-I forms with lecithin/cholesterol acyltransferase (LCAT). Mutations in these proteins either prevent or impair the formation and possibly the functionality of HDL. Remodeling and catabolism of HDL is the result of interactions of HDL with cell receptors and other membrane and plasma proteins including hepatic lipase (HL), endothelial lipase (EL), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), apolipoprotein M (apoM), scavenger receptor class B type I (SR-BI), ATP-binding cassette transporter G1 (ABCG1), the F1 subunit of ATPase (Ecto F1-ATPase), and the cubulin/megalin receptor. Similarly to apoA-I, apolipoprotein E and apolipoprotein A-IV were shown to form discrete HDL particles containing these apolipoproteins which may have important but still unexplored functions. Furthermore, several plasma proteins were found associated with HDL and may modulate its biological functions. The effect of these proteins on the functionality of HDL is the topic of ongoing research.

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Section: 7mentioning

confidence: 97%

Section: 7mentioning

confidence: 98%

HDL Biogenesis, Remodeling, and Catabolism

Zannis

Fotakis

Κούκος

et al. 2014

Handbook of Experimental Pharmacology

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“…Circulating levels of blood lipids are consistently associated with the risk of CHD (Genoux et al, 2013). The lipid levels are affected by different genetic and acquired factors.…”

Section: Discussionmentioning

confidence: 99%

Significant interaction of APOE rs4420638 polymorphism with HDL-C and APOA-I levels in coronary heart disease in Han Chinese men

Huang

Gao

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Apolipoprotein E (APOE) is recognized for its importance in lipoprotein metabolism and cardiovascular disease. We evaluated the association between APOE rs4420638 genotypes and circulating lipid concentrations along with the risk of coronary heart disease (CHD). We conducted a case-control study involving 1508 individuals to investigate the contribution of rs4420638 to the risk of CHD in Han Chinese. In addition, we performed a meta-analysis to evaluate the association between rs4420638 and CHD in Europeans and Asians. The results show that rs4420638 is significantly correlated with increased CHD risk in male Han Chinese [P = 0.040, odds ratio (OR) = 1.34, 95% confidential interval (95%CI) = 1.01-1.78] and is likely to increase the risk of CHD under the dominant model in males (P = 13415 rs4420638 and CHD in Han Chinese men ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 13414-13424 (2015) 0.036, OR = 1.38, 95%CI = 1.02-1.88). A further subgroup analysis by rs4420638 genotype found a significant association of rs4420638 AA with high-density lipoprotein cholesterol (HDL-C) (P = 0.012) and APOA-I levels (P = 0.0001) in males. The meta-analysis suggests that rs4420638 significantly increases the risk of CHD (OR = 1.18, 95%CI = 1.14-1.22, P < 0.0001, fixed-effect method). Our case-control study shows that rs4420638 genotype AA has a significant association with the concentrations of circulating HDL-C and APOA-I in CHD in Han Chinese males. The meta-analysis suggests that rs4420638 is associated with CHD risk in Europeans and Asians.

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“…In mice, the knock-out of P2Y13, which activates hepatic HDL uptake, impaired RCT from macrophage to feces and enhanced atherosclerosis despite counter-balanced SR-BI upregulation [40 & ]. The potential clinical relevance of this F1-ATPase/ P2Ys axis in humans is indicated by the identification of serum F1-ATPase inhibitor (IF1) as an independent determinant of HDL-C and coronary heart disease (CHD) risk [41].…”

Section: Cellular Uptake Of Hdls or Hdl Componentsmentioning

confidence: 99%

HDLs in crises

Eckardstein

Rohrer

2016

Current Opinion in Lipidology

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Any successful clinical exploitation of HDLs will depend on the identification of the most relevant (dys)functions and their structural correlates. Stringent or prioritized structure-(dys)function relationships may provide biomarkers for better risk assessment and monitoring of treatment response. The most relevant agonists carried by either functional or dysfunctional HDLs as well as their cellular responders are interesting targets for drug development.

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Serum IF1 concentration is independently associated to HDL levels and to coronary heart disease: the GENES study

Cited by 31 publications

References 39 publications

HDL Biogenesis, Remodeling, and Catabolism

HDL Biogenesis, Remodeling, and Catabolism

Significant interaction of APOE rs4420638 polymorphism with HDL-C and APOA-I levels in coronary heart disease in Han Chinese men

HDLs in crises

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