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Nat Rev Cardiol. 2016 Jan;13(1):48-60. doi: 10.1038/nrcardio.2015.124. Epub 2015 Sep 1.

Dysfunctional HDL and atherosclerotic cardiovascular disease.

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Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington, DC, USA.
Cardiology Department, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Centre for Vascular Research at the University of New South Wales, Sydney, Australia.
National Institute for Health and Medical Research at Pitié-Salpétrière University Hospital, Paris, France.
Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA, USA.
INSERM-ICAN Research Unit 1166 of the National Institute for Health and Medical Research at Pitié-Salpétrière University Hospital, Paris, France.
Department of Medicine, Columbia University, New York, NY, USA.
Pharmacology &Nutritional Sciences and Saha Cardiovascular Research Center, University of Kentucky College of Medicine, Lexington, KY, USA.


High-density lipoproteins (HDLs) protect against atherosclerosis by removing excess cholesterol from macrophages through the ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) pathways involved in reverse cholesterol transport. Factors that impair the availability of functional apolipoproteins or the activities of ABCA1 and ABCG1 could, therefore, strongly influence atherogenesis. HDL also inhibits lipid oxidation, restores endothelial function, exerts anti-inflammatory and antiapoptotic actions, and exerts anti-inflammatory actions in animal models. Such properties could contribute considerably to the capacity of HDL to inhibit atherosclerosis. Systemic and vascular inflammation has been proposed to convert HDL to a dysfunctional form that has impaired antiatherogenic effects. A loss of anti-inflammatory and antioxidative proteins, perhaps in combination with a gain of proinflammatory proteins, might be another important component in rendering HDL dysfunctional. The proinflammatory enzyme myeloperoxidase induces both oxidative modification and nitrosylation of specific residues on plasma and arterial apolipoprotein A-I to render HDL dysfunctional, which results in impaired ABCA1 macrophage transport, the activation of inflammatory pathways, and an increased risk of coronary artery disease. Understanding the features of dysfunctional HDL or apolipoprotein A-I in clinical practice might lead to new diagnostic and therapeutic approaches to atherosclerosis.

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