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