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Atrial fibrillation is associated with alterations in HDL function, metabolism, and particle number

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Abstract

Increased morbidity and mortality in atrial fibrillation (AF) are related to the pro-fibrotic, pro-thrombotic, and pro-inflammatory processes that underpin the disease. High-density lipoproteins (HDL) have anti-inflammatory, anti-oxidative, and anti-thrombotic properties. Functional impairment of HDL may, therefore, associate with AF initiation or progression. We studied indices of HDL quality and quantity of AF patients and healthy controls, including HDL-particle number, HDL cholesterol, apolipoprotein (apo) A–I levels, serum amyloid A (SAA) content and HDL-cholesterol efflux capacity, and paraoxonase activity of apoB-depleted serum. Serum samples were collected from AF patients (n = 91) before catheter ablation and from age- and sex-matched control subjects (n = 54). HDL-cholesterol efflux capacity was assessed in a validated assay using [3H]-cholesterol-labeled J774 macrophages. Lecithin–cholesterol acyltransferase (LCAT) and paraoxonase activities were assessed using fluorometric assays, SAA levels were determined by ELISA, and total and subclass HDL-particle number was assessed by nuclear magnetic resonance spectroscopy. ApoA-I levels were determined by immunoturbidimetry. HDL-cholesterol efflux capacity, HDL-particle number, apoA-I levels, and LCAT activity were markedly reduced in AF patients when compared to healthy individuals (all p < 0.001), whereas HDL-associated paraoxonase activity and SAA content were not altered (p = 0.578, p = 0.681). Notably, cholesterol efflux capacity, HDL-particle number, apoA-I levels as well as LCAT activity recovered following restoration of sinus rhythm (all p < 0.001). We identified marked alterations in HDL function, HDL maturation, and HDL-particle number in AF patients. Assessing HDL-particle number and function in AF may be used as a surrogate marker of AF onset and progression and may help identifying patients at high risk.

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Funding

This work was supported by the Austrian Science Fund FWF (FWF W1241, DK-MOLIN, and P22976-B18 to GM). PB and DH were supported by the Volkswagen Foundation Germany through the Lichtenberg professorship program to DH (#84901)

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Author notes

  1. Markus Trieb and Jelena Kornej contributed equally to this work.

  2. Gunther Marsche and Petra Buettner contributed equally to this work.

Authors and Affiliations

  1. Department of Electrophysiology, Heart Center Leipzig-University Hospital of Cardiology, Leipzig, Germany

    Jelena Kornej, Gerhard Hindricks, Philipp Sommer, Nikolaos Dagres, Borislav Dinov, Andreas Bollmann, Daniela Husser & Petra Buettner

  2. Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Universitätsplatz 4, 8010, Graz, Austria

    Markus Trieb, Eva Knuplez & Gunther Marsche

  3. Department of Internal Medicine/Cardiology, Heart Center Leipzig-University Hospital of Cardiology, Strümpellstr. 39, 04289, Leipzig, Germany

    Holger Thiele & Petra Buettner

  4. BioTechMed-Graz, Graz, Austria

    Markus Trieb & Gunther Marsche

  5. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria

    Hubert Scharnagl

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  1. Markus Trieb
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Correspondence to Gunther Marsche or Petra Buettner.

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Trieb, M., Kornej, J., Knuplez, E. et al. Atrial fibrillation is associated with alterations in HDL function, metabolism, and particle number. Basic Res Cardiol 114, 27 (2019). https://doi.org/10.1007/s00395-019-0735-0

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