Biological Consequences of Dysfunctional HDL

Author(s): Angela Pirillo*, Alberico Luigi Catapano*, Giuseppe Danilo Norata

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 9 , 2019

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Epidemiological studies have suggested an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and the risk of cardiovascular disease. HDLs promote reverse cholesterol transport (RCT) and possess several putative atheroprotective functions, associated to the anti-inflammatory, anti-thrombotic and anti-oxidant properties as well as to the ability to support endothelial physiology.

The assumption that increasing HDL-C levels would be beneficial on cardiovascular disease (CVD), however, has been questioned as, in most clinical trials, HDL-C-raising therapies did not result in improved cardiovascular outcomes. These findings, together with the observations from Mendelian randomization studies showing that polymorphisms mainly or solely associated with increased HDL-C levels did not decrease the risk of myocardial infarction, shift the focus from HDL-C levels toward HDL functional properties. Indeed, HDL from atherosclerotic patients not only exhibit impaired atheroprotective functions but also acquire pro-atherogenic properties and are referred to as “dysfunctional” HDL; this occurs even in the presence of normal or elevated HDL-C levels. Pharmacological approaches aimed at restoring HDL functions may therefore impact more significantly on CVD outcome than drugs used so far to increase HDL-C levels. The aim of this review is to discuss the pathological conditions leading to the formation of dysfunctional HDL and their role in atherosclerosis and beyond.

Keywords: High density lipoprotein, dysfunctional HDL, HDL quality, HDL subfractions, atherosclerosis, cardiovascular disease, epidemiological studies, apolipoprotein-A.

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Year: 2019
Page: [1644 - 1664]
Pages: 21
DOI: 10.2174/0929867325666180530110543
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