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Molecular mechanisms of vascular effects of High-density lipoprotein: alterations in cardiovascular disease.

Besler C, Lüscher TF, Landmesser U - EMBO Mol Med (2012)

Bottom Line: Studies in gene-targeted mice, however, have also indicated that increasing HDL-cholesterol plasma levels can either limit (e.g. apolipoprotein A-I) or accelerate (e.g. Scavenger receptor class B type I) atherosclerosis.Moreover, vascular effects of HDL have been observed to be heterogenous and are altered in patients with CAD or diabetes, a condition that has been termed 'HDL dysfunction'.It will therefore be important to further determine, which biological functions of HDL are critical for its anti-atherosclerotic properties, as well as how these can be measured and targeted.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.

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Related in: MedlinePlus

Alterations of the atheroprotective effects of HDL in patients with CADModification of apoA-I by MPO has been shown to impair the macrophage cholesterol efflux capacity of HDL. More recently, accumulation of MDA in HDL from patients with CAD due to an impaired HDL-associated PON1 activity has been observed to stimulate activation of endothelial PKCbeta-II via the LOX-1 receptor. PKCbeta-II activation by HDL from patients with CAD inhibited Akt-dependent phosphorylation of eNOS at serine residue 1177 and increased the inhibitory eNOS phosphorylation at threonine 495, leading to reduced endothelial NO production.
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fig04: Alterations of the atheroprotective effects of HDL in patients with CADModification of apoA-I by MPO has been shown to impair the macrophage cholesterol efflux capacity of HDL. More recently, accumulation of MDA in HDL from patients with CAD due to an impaired HDL-associated PON1 activity has been observed to stimulate activation of endothelial PKCbeta-II via the LOX-1 receptor. PKCbeta-II activation by HDL from patients with CAD inhibited Akt-dependent phosphorylation of eNOS at serine residue 1177 and increased the inhibitory eNOS phosphorylation at threonine 495, leading to reduced endothelial NO production.

Mentions: Oxidative modifications of apoA-I have been shown to impair the cholesterol efflux capacity of HDL (Fig 4). In particular, myeloperoxidase (MPO), a hypochlorous acid (HOCl)-generating enzyme that is enriched in human atheroma, can modify apoA-I and induce chloro- and nitrotyrosine formation (Zheng et al, 2004) as well as methionine oxidation (Shao et al, 2008). Modification of HDL by MPO leads to a profound impairment of the cholesterol efflux capacity of HDL (Bergt et al, 2004; Zheng et al, 2004) and an impaired capacity of HDL to stimulate endothelial NO production (Sorrentino et al, 2010). Interestingly, nitro-and chloro-tyrosine levels of apoA-I are higher in patients with CAD as compared to healthy subjects (Zheng et al, 2004). However, there is an ongoing controversy about the mechanisms whereby MPO modification renders apoA-I dysfunctional.


Molecular mechanisms of vascular effects of High-density lipoprotein: alterations in cardiovascular disease.

Besler C, Lüscher TF, Landmesser U - EMBO Mol Med (2012)

Alterations of the atheroprotective effects of HDL in patients with CADModification of apoA-I by MPO has been shown to impair the macrophage cholesterol efflux capacity of HDL. More recently, accumulation of MDA in HDL from patients with CAD due to an impaired HDL-associated PON1 activity has been observed to stimulate activation of endothelial PKCbeta-II via the LOX-1 receptor. PKCbeta-II activation by HDL from patients with CAD inhibited Akt-dependent phosphorylation of eNOS at serine residue 1177 and increased the inhibitory eNOS phosphorylation at threonine 495, leading to reduced endothelial NO production.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376856&req=5

fig04: Alterations of the atheroprotective effects of HDL in patients with CADModification of apoA-I by MPO has been shown to impair the macrophage cholesterol efflux capacity of HDL. More recently, accumulation of MDA in HDL from patients with CAD due to an impaired HDL-associated PON1 activity has been observed to stimulate activation of endothelial PKCbeta-II via the LOX-1 receptor. PKCbeta-II activation by HDL from patients with CAD inhibited Akt-dependent phosphorylation of eNOS at serine residue 1177 and increased the inhibitory eNOS phosphorylation at threonine 495, leading to reduced endothelial NO production.
Mentions: Oxidative modifications of apoA-I have been shown to impair the cholesterol efflux capacity of HDL (Fig 4). In particular, myeloperoxidase (MPO), a hypochlorous acid (HOCl)-generating enzyme that is enriched in human atheroma, can modify apoA-I and induce chloro- and nitrotyrosine formation (Zheng et al, 2004) as well as methionine oxidation (Shao et al, 2008). Modification of HDL by MPO leads to a profound impairment of the cholesterol efflux capacity of HDL (Bergt et al, 2004; Zheng et al, 2004) and an impaired capacity of HDL to stimulate endothelial NO production (Sorrentino et al, 2010). Interestingly, nitro-and chloro-tyrosine levels of apoA-I are higher in patients with CAD as compared to healthy subjects (Zheng et al, 2004). However, there is an ongoing controversy about the mechanisms whereby MPO modification renders apoA-I dysfunctional.

Bottom Line: Studies in gene-targeted mice, however, have also indicated that increasing HDL-cholesterol plasma levels can either limit (e.g. apolipoprotein A-I) or accelerate (e.g. Scavenger receptor class B type I) atherosclerosis.Moreover, vascular effects of HDL have been observed to be heterogenous and are altered in patients with CAD or diabetes, a condition that has been termed 'HDL dysfunction'.It will therefore be important to further determine, which biological functions of HDL are critical for its anti-atherosclerotic properties, as well as how these can be measured and targeted.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.

Show MeSH
Related in: MedlinePlus