Myeloperoxidase: an inflammatory enzyme for generating dysfunctional high density lipoprotein

Area of Science:

• Cardiovascular Science
• Biochemistry
• Molecular Biology

Background:

• High-density lipoprotein (HDL) is recognized for its cardioprotective effects, involving mechanisms like cholesterol efflux via the ATP-binding cassette transporter A1 (ABCA1).
• HDL's anti-inflammatory and antioxidant properties also contribute to inhibiting atherosclerosis.

Purpose of the Study:

• To investigate the role of myeloperoxidase (MPO) in HDL oxidation.
• To understand how MPO-mediated oxidation affects HDL's function, particularly its interaction with ABCA1.
• To explore the therapeutic potential of targeting MPO and the diagnostic utility of oxidized HDL.

Main Methods:

• Analysis of mutated apolipoprotein A-I (apoA-I) forms.
• Treatment of oxidized apoA-I with methionine sulfoxide reductase.
• Examination of the crystal structure of lipid-free apoA-I.

Main Results:

• Myeloperoxidase targets HDL for oxidation, leading to dysfunctional HDL.
• MPO-dependent oxidation of apoA-I impairs cholesterol removal via the ABCA1 pathway.
• Oxidation of specific tyrosine and methionine residues in apoA-I disrupts its interaction with ABCA1, potentially by altering protein conformation and surface charge.

Conclusions:

• HDL oxidation by MPO may convert the cardioprotective lipoprotein into a dysfunctional form.
• MPO emerges as a potential therapeutic target for preventing vascular diseases.
• Oxidized HDL may serve as a valuable blood marker for clinically significant cardiovascular disease.