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High-density lipoproteins and endothelial functions: Mechanistic insights and alterations in cardiovascular disease


Riwanto, Meliana; Landmesser, Ulf (2013). High-density lipoproteins and endothelial functions: Mechanistic insights and alterations in cardiovascular disease. Journal of Lipid Research, 54(12):3227-3243.

Abstract

Prospective studies of cardiovascular risk-factors have shown that reduced plasma levels of HDL-cholesterol are associated with increased risk of coronary-disease. Experimental and translational studies have revealed several potential anti-atherogenic effects of HDL, including protective effects of HDL on endothelial cell functions. HDL has been suggested to protect endothelial cell functions by preventing oxidation of LDL and its adverse endothelial effects. Moreover, HDL from healthy subjects can directly stimulate endothelial cell production of nitric-oxide, anti-inflammatory, anti-apoptotic, anti-thrombotic effects, and endothelial-repair processes. Recent clinical-trials using HDL-cholesterol raising agents, such as torcetrapib, dalcetrapib and niacin, could not observe significant reduction of cardiovascular events in patients with coronary-disease. Growing evidence suggests that vascular effects of HDL are highly heterogenous and vasoprotective properties of HDL are altered in patients with coronary-disease. Notably, in recent studies no clear association of higher HDL-cholesterol levels with reduced risk of cardiovascular events was observed in patients with established coronary-disease. Greater understanding of mechanisms of action of HDL and its altered vascular effects is therefore crucial within the context of HDL-targeted therapies. In this review, we will address different effects of HDL on endothelial cell functions potentially relevant to atherosclerotic vascular disease and explore molecular mechanisms leading to dysfunctional HDL.

Prospective studies of cardiovascular risk-factors have shown that reduced plasma levels of HDL-cholesterol are associated with increased risk of coronary-disease. Experimental and translational studies have revealed several potential anti-atherogenic effects of HDL, including protective effects of HDL on endothelial cell functions. HDL has been suggested to protect endothelial cell functions by preventing oxidation of LDL and its adverse endothelial effects. Moreover, HDL from healthy subjects can directly stimulate endothelial cell production of nitric-oxide, anti-inflammatory, anti-apoptotic, anti-thrombotic effects, and endothelial-repair processes. Recent clinical-trials using HDL-cholesterol raising agents, such as torcetrapib, dalcetrapib and niacin, could not observe significant reduction of cardiovascular events in patients with coronary-disease. Growing evidence suggests that vascular effects of HDL are highly heterogenous and vasoprotective properties of HDL are altered in patients with coronary-disease. Notably, in recent studies no clear association of higher HDL-cholesterol levels with reduced risk of cardiovascular events was observed in patients with established coronary-disease. Greater understanding of mechanisms of action of HDL and its altered vascular effects is therefore crucial within the context of HDL-targeted therapies. In this review, we will address different effects of HDL on endothelial cell functions potentially relevant to atherosclerotic vascular disease and explore molecular mechanisms leading to dysfunctional HDL.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:18 Nov 2013 16:03
Last Modified:05 Apr 2016 17:05
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0022-2275
Additional Information:This research was originally published in Journal of Lipid Research. Riwanto, Meliana; Landmesser, Ulf (2013). High-density lipoproteins and endothelial functions: Mechanistic insights and alterations in cardiovascular disease. Journal of Lipid Research, 54(12):3227-3243. © the American Society for Biochemistry and Molecular Biology.
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1194/jlr.R037762
PubMed ID:23873269
Permanent URL: https://doi.org/10.5167/uzh-83897

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