Dysfunctional high-density lipoprotein.

Area of Science:

• Cardiovascular Research
• Lipid Metabolism
• Biochemistry

Background:

• High-density lipoprotein (HDL) is traditionally recognized for its cardioprotective properties.
• Emerging evidence suggests HDL can become dysfunctional, losing its protective role and potentially contributing to atherosclerosis.
• The precise mechanisms and structural changes leading to HDL dysfunction are not fully understood.

Purpose of the Study:

• To review the current understanding of dysfunctional high-density lipoprotein (HDL).
• To explore the mechanisms by which HDL loses its atheroprotective function.
• To highlight the role of specific enzymes in HDL modification.

Main Methods:

• Review of recent scientific literature on HDL modification.
• Analysis of studies investigating the role of myeloperoxidase (MPO) in HDL dysfunction.
• Examination of the impact of MPO-mediated oxidation on HDL structure and function.

Main Results:

• HDL's protective role is not absolute; it can become atherogenic under specific conditions.
• Myeloperoxidase (MPO) plays a significant role in generating dysfunctional HDL in vivo.
• MPO oxidizes apolipoprotein A-I in HDL, impairing cholesterol efflux via ATP-binding cassette transporter A1 and promoting atherosclerosis.

Conclusions:

• HDL can paradoxically promote atherosclerosis, challenging its established atheroprotective status.
• Myeloperoxidase-associated modification is identified as a potential key mechanism driving HDL dysfunction.
• Further research is crucial to elucidate in vivo HDL modification pathways and develop targeted therapies.