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Published on: October 12, 2017
The antiatherogenic function of HDL is impaired in hyperhomocysteinemic subjects
Kirsten B Holven1, Pål Aukrust, Kjetil Retterstøl
1Institute for Basic Medical Sciences, Department of Nutrition, University of Oslo, Blindern, 0316 Oslo, Norway. kirsten.holven@medisin.uio.no
Insights
High homocysteine levels impair high-density lipoprotein (HDL) function, reducing its ability to remove cholesterol and fight inflammation. This dysfunction in HDL may explain increased cardiovascular disease risk in hyperhomocysteinemic individuals.
Area of Science:
- Cardiovascular Science
- Metabolic Disorders
- Lipid Metabolism
Background:
- High plasma homocysteine is linked to cardiovascular disease risk.
- Plasma high-density lipoprotein (HDL) concentration is inversely correlated with cardiovascular disorders.
- Dysfunctional HDL may contribute to cardiovascular events in hyperhomocysteinemic individuals.
Purpose of the Study:
- To investigate the functionality of HDL in hyperhomocysteinemic subjects.
- To determine if serum from hyperhomocysteinemic individuals impairs cholesterol efflux and inflammatory mediator release.
- To assess the antiatherogenic activity of HDL in relation to homocysteine levels.
Main Methods:
- Serum analysis from hyperhomocysteinemic (n=10) and control (n=10) subjects.
- Assessed serum's ability to induce cholesterol efflux from macrophages.
- Evaluated serum's effect on inflammatory mediator release from endothelial cells.
- Measured paraoxonase activity in serum.
Main Results:
- Serum from hyperhomocysteinemic subjects showed impaired cholesterol efflux.
- HDL from these subjects had reduced anti-inflammatory effects on endothelial cells.
- Paraoxonase activity was significantly reduced in hyperhomocysteinemic individuals.
- Attenuated suppression of interleukin-6 and growth-related oncogene-alpha release was observed.
Conclusions:
- Hyperhomocysteinemic individuals exhibit dysfunctional HDL particles.
- Dysfunctional HDL has attenuated antiatherogenic activity.
- This HDL dysfunction offers a potential explanation for increased cardiovascular risk in hyperhomocysteinemia.
Abstract:
High plasma homocysteine concentrations have been associated with increased risk of cardiovascular disease, whereas plasma HDL concentration is inversely correlated to such disorders. We hypothesized that hyperhomocysteinemic subjects may have dysfunctional HDL. We therefore investigated the ability of serum from hyperhomocysteinemic male and female subjects (n = 10) and control subjects (n = 10) to induce cholesterol efflux and to inhibit release of inflammatory mediators from human umbilical vein endothelial cell. We found that serum from hyperhomocysteinemic subjects had impaired ability to induce cholesterol efflux from lipid-loaded macrophages compared with healthy controls. HDL from those with markedly raised homocysteine concentrations had a reduced antiinflammatory effect in tumor necrosis factor-alpha-activated endothelial cells with an attenuated suppressive effect on interleukin-6 growth-related oncogene-alpha release. Also, the activity of paraoxonase in serum, a multifunctional enzyme with antioxidative effects in relation to the function of HDL, was significantly reduced in hyperhomocysteinemic subjects, in particular those with markedly raised homocysteine concentration. Our findings suggest that hyperhomocysteinemic individuals have dysfunctional HDL particles with attenuated antiatherogenic activity and may represent a novel explanation for the increased risk of cardiovascular events in these individuals.
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