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Published on: October 12, 2017
Dysfunctional HDL and atherosclerotic cardiovascular disease
Robert S Rosenson1, H Bryan Brewer2, Benjamin J Ansell3
1Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Insights
High-density lipoproteins (HDL) combat atherosclerosis by removing cholesterol. Inflammation can make HDL dysfunctional, impairing its protective effects and increasing heart disease risk.
Area of Science:
- Cardiovascular Biology
- Lipid Metabolism
- Atherosclerosis Research
Background:
- High-density lipoproteins (HDL) are crucial in preventing atherosclerosis via reverse cholesterol transport.
- HDL possesses anti-inflammatory, antioxidative, and endothelial function-restoring properties that inhibit disease progression.
- Systemic and vascular inflammation are implicated in converting HDL into a dysfunctional state.
Purpose of the Study:
- To elucidate the mechanisms by which HDL becomes dysfunctional.
- To understand the role of inflammation and specific enzymes in HDL dysfunction.
- To explore the clinical implications of dysfunctional HDL in atherosclerosis.
Main Methods:
- Investigated the role of ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1) in HDL function.
- Examined the impact of inflammation on HDL's antiatherogenic properties.
- Studied the effects of myeloperoxidase on apolipoprotein A-I and HDL functionality.
Main Results:
- Dysfunctional HDL exhibits impaired cholesterol transport via ABCA1 and ABCG1 pathways.
- Inflammation leads to a loss of protective proteins and gain of pro-inflammatory proteins in HDL.
- Myeloperoxidase-induced modifications of apolipoprotein A-I render HDL dysfunctional, increasing coronary artery disease risk.
Conclusions:
- Inflammation-induced HDL dysfunction significantly contributes to atherogenesis.
- Understanding HDL and apolipoprotein A-I dysfunction offers potential for new diagnostic and therapeutic strategies.
- Targeting HDL dysfunction may provide novel approaches to managing atherosclerosis and coronary artery disease.
Abstract:
High-density lipoproteins (HDLs) protect against atherosclerosis by removing excess cholesterol from macrophages through the ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) pathways involved in reverse cholesterol transport. Factors that impair the availability of functional apolipoproteins or the activities of ABCA1 and ABCG1 could, therefore, strongly influence atherogenesis. HDL also inhibits lipid oxidation, restores endothelial function, exerts anti-inflammatory and antiapoptotic actions, and exerts anti-inflammatory actions in animal models. Such properties could contribute considerably to the capacity of HDL to inhibit atherosclerosis. Systemic and vascular inflammation has been proposed to convert HDL to a dysfunctional form that has impaired antiatherogenic effects. A loss of anti-inflammatory and antioxidative proteins, perhaps in combination with a gain of proinflammatory proteins, might be another important component in rendering HDL dysfunctional. The proinflammatory enzyme myeloperoxidase induces both oxidative modification and nitrosylation of specific residues on plasma and arterial apolipoprotein A-I to render HDL dysfunctional, which results in impaired ABCA1 macrophage transport, the activation of inflammatory pathways, and an increased risk of coronary artery disease. Understanding the features of dysfunctional HDL or apolipoprotein A-I in clinical practice might lead to new diagnostic and therapeutic approaches to atherosclerosis.
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