Biological consequences of dysfunctional HDL

Angela Pirillo, Alberico Luigi Catapano, Giuseppe Danilo Norata

Research output: Contribution to journalArticle

Abstract

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. Aims of this review is to discuss the pathological conditions leading to the formation of dysfunctional HDL and their role in atherosclerosis and beyond.

Original languageEnglish
JournalCurrent Medicinal Chemistry
DOIs
Publication statusE-pub ahead of print - May 29 2018

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HDL Lipoproteins
Cardiovascular Diseases
Physiology
Random Allocation
Polymorphism
Oxidants
HDL Cholesterol
Epidemiologic Studies
Atherosclerosis
Anti-Inflammatory Agents
Myocardial Infarction
Cholesterol
Clinical Trials
Pharmacology

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Biological consequences of dysfunctional HDL. / Pirillo, Angela; Catapano, Alberico Luigi; Norata, Giuseppe Danilo.

In: Current Medicinal Chemistry, 29.05.2018.

Research output: Contribution to journalArticle

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AB - 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. Aims of this review is to discuss the pathological conditions leading to the formation of dysfunctional HDL and their role in atherosclerosis and beyond.

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