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Dysfunctional HDL: from structure-function-relationships to biomarkers


Riwanto, Meliana; Rohrer, Lucia; von Eckardstein, Arnold; Landmesser, Ulf (2015). Dysfunctional HDL: from structure-function-relationships to biomarkers. In: von Eckardstein, Arnold; Kardassis, Dimitris. High Density Lipoproteins : From Biological Understanding to Clinical Exploitation. Berlin Heidelberg New York: Springer, 337-366.

Abstract

Reduced plasma levels of HDL-C are associated with an increased risk of CAD and myocardial infarction, as shown in various prospective population studies. However, recent clinical trials on lipid-modifying drugs that increase plasma levels of HDL-C have not shown significant clinical benefit. Notably, in some recent clinical studies, there is no clear association of higher HDL-C levels with a reduced risk of cardiovascular events observed in patients with existing CAD. These observations have prompted researchers to shift from a cholesterol-centric view of HDL towards assessing the function and composition of HDL particles. Of importance, experimental and translational studies have further demonstrated various potential antiatherogenic effects of HDL. HDL has been proposed to promote macrophage reverse cholesterol transport and to protect endothelial cell functions by prevention of oxidation of LDL and its adverse endothelial effects. Furthermore, HDL from healthy subjects can directly stimulate endothelial cell production of nitric oxide and exert anti-inflammatory and antiapoptotic effects. Of note, increasing evidence suggests that the vascular effects of HDL can be highly heterogeneous and HDL may lose important anti-atherosclerotic properties and turn dysfunctional in patients with chronic inflammatory disorders. A greater understanding of mechanisms of action of HDL and its altered vascular effects is therefore critical within the context of HDL-targeted therapies.

Abstract

Reduced plasma levels of HDL-C are associated with an increased risk of CAD and myocardial infarction, as shown in various prospective population studies. However, recent clinical trials on lipid-modifying drugs that increase plasma levels of HDL-C have not shown significant clinical benefit. Notably, in some recent clinical studies, there is no clear association of higher HDL-C levels with a reduced risk of cardiovascular events observed in patients with existing CAD. These observations have prompted researchers to shift from a cholesterol-centric view of HDL towards assessing the function and composition of HDL particles. Of importance, experimental and translational studies have further demonstrated various potential antiatherogenic effects of HDL. HDL has been proposed to promote macrophage reverse cholesterol transport and to protect endothelial cell functions by prevention of oxidation of LDL and its adverse endothelial effects. Furthermore, HDL from healthy subjects can directly stimulate endothelial cell production of nitric oxide and exert anti-inflammatory and antiapoptotic effects. Of note, increasing evidence suggests that the vascular effects of HDL can be highly heterogeneous and HDL may lose important anti-atherosclerotic properties and turn dysfunctional in patients with chronic inflammatory disorders. A greater understanding of mechanisms of action of HDL and its altered vascular effects is therefore critical within the context of HDL-targeted therapies.

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Additional indexing

Item Type:Book Section, not refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
Dewey Decimal Classification:610 Medicine & health
540 Chemistry
Language:English
Date:2015
Deposited On:25 Jan 2016 12:47
Last Modified:05 Apr 2016 20:00
Publisher:Springer
Series Name:Handbook of Experimental Pharmacology
Number:224
ISSN:0171-2004
ISBN:978-3-319-09664-3
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1007/978-3-319-09665-0_10
PubMed ID:25522994

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