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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

Molecular biosynthesis of HDLLipid-free apoA-I is secreted by the liver and intestine and acquires phospholipids and free cholesterol via hepatic and intestinal ABCA-1. Nascent HDL takes up further phospholipids (via PLTP) as well as free cholesterol from peripheral tissues and triglyceride-rich lipoproteins. HDL-associated LCAT esterifies part of the free cholesterol to cholesterol esters, thereby forming the hydrophobic core of the HDL particle (‘HDL maturation’). HDL-associated cholesterol is either directly transferred to the liver via hepatic SR-BI or following CETP-mediated transfer to VLDL/LDL via the hepatic LDL receptor.
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fig01: Molecular biosynthesis of HDLLipid-free apoA-I is secreted by the liver and intestine and acquires phospholipids and free cholesterol via hepatic and intestinal ABCA-1. Nascent HDL takes up further phospholipids (via PLTP) as well as free cholesterol from peripheral tissues and triglyceride-rich lipoproteins. HDL-associated LCAT esterifies part of the free cholesterol to cholesterol esters, thereby forming the hydrophobic core of the HDL particle (‘HDL maturation’). HDL-associated cholesterol is either directly transferred to the liver via hepatic SR-BI or following CETP-mediated transfer to VLDL/LDL via the hepatic LDL receptor.

Mentions: Apolipoprotein A-I is the main protein constituent of HDL in plasma (Fig 1). To date, more than 40 genetic defects of apoA-I have been described (Schaefer et al, 2010). However, the consequences of these defects with regard to cardiovascular risk have remained inconclusive, largely because of the limited number of carriers of apoA-I gene defects. Notably, in one of the larger studies involving 54 heterozygotes for the apoA-I mutation L178P, carriers of the apoA-I gene defect had lower plasma levels of HDL cholesterol, impaired endothelial function, and increased carotid intima-media thickness (IMT) when compared to non-affected family controls (Hovingh et al, 2004). Notably, however, several apoA-I variants with amino acid substitutions have also been associated with amyloidosis (Schaefer et al, 2010), and amyloidosis has also been suggested to lead to endothelial dysfunction and increased carotid IMT (Modesto et al, 2007).


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

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

Molecular biosynthesis of HDLLipid-free apoA-I is secreted by the liver and intestine and acquires phospholipids and free cholesterol via hepatic and intestinal ABCA-1. Nascent HDL takes up further phospholipids (via PLTP) as well as free cholesterol from peripheral tissues and triglyceride-rich lipoproteins. HDL-associated LCAT esterifies part of the free cholesterol to cholesterol esters, thereby forming the hydrophobic core of the HDL particle (‘HDL maturation’). HDL-associated cholesterol is either directly transferred to the liver via hepatic SR-BI or following CETP-mediated transfer to VLDL/LDL via the hepatic LDL receptor.
© Copyright Policy
Related In: Results  -  Collection

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

fig01: Molecular biosynthesis of HDLLipid-free apoA-I is secreted by the liver and intestine and acquires phospholipids and free cholesterol via hepatic and intestinal ABCA-1. Nascent HDL takes up further phospholipids (via PLTP) as well as free cholesterol from peripheral tissues and triglyceride-rich lipoproteins. HDL-associated LCAT esterifies part of the free cholesterol to cholesterol esters, thereby forming the hydrophobic core of the HDL particle (‘HDL maturation’). HDL-associated cholesterol is either directly transferred to the liver via hepatic SR-BI or following CETP-mediated transfer to VLDL/LDL via the hepatic LDL receptor.
Mentions: Apolipoprotein A-I is the main protein constituent of HDL in plasma (Fig 1). To date, more than 40 genetic defects of apoA-I have been described (Schaefer et al, 2010). However, the consequences of these defects with regard to cardiovascular risk have remained inconclusive, largely because of the limited number of carriers of apoA-I gene defects. Notably, in one of the larger studies involving 54 heterozygotes for the apoA-I mutation L178P, carriers of the apoA-I gene defect had lower plasma levels of HDL cholesterol, impaired endothelial function, and increased carotid intima-media thickness (IMT) when compared to non-affected family controls (Hovingh et al, 2004). Notably, however, several apoA-I variants with amino acid substitutions have also been associated with amyloidosis (Schaefer et al, 2010), and amyloidosis has also been suggested to lead to endothelial dysfunction and increased carotid IMT (Modesto et al, 2007).

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