Molecular mechanisms of vascular effects of High-density lipoprotein: alterations in cardiovascular disease.
Bottom Line: Moreover, experimental studies have identified potential anti-atherogenic properties of HDL, including promotion of macrophage cholesterol efflux and direct endothelial-protective effects of HDL, such as stimulation of endothelial nitric oxide production and repair, anti-apoptotic, anti-inflammatory and anti-thrombotic properties.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.
Affiliation: Department of Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.Show MeSH
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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).
Affiliation: Department of Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.