Oxidized phospholipid content destabilizes the structure of reconstituted high density lipoprotein particles and...

Area of Science:

• Cardiovascular Biology
• Lipid Metabolism
• Protein Chemistry

Background:

• High-density lipoprotein (HDL) particles, crucial for reverse cholesterol transport and possessing athero-protective functions, are composed of lipids and proteins, with apolipoprotein A-I (apoA-I) being a key component.
• Dysfunctional HDL, characterized by increased oxidized phospholipid (Ox-PL) content, loses its beneficial properties and can promote inflammation and atherosclerosis.
• Paraoxonase 1 (PON1), an enzyme associated with HDL, contributes significantly to HDL's anti-inflammatory and anti-atherogenic activities.

Purpose of the Study:

• To investigate the molecular mechanisms by which Ox-PLs alter the physicochemical properties of HDL particles.
• To characterize the impact of varying Ox-PL content on reconstituted HDL (rHDL) particles.
• To assess the effect of Ox-PL-induced modifications on the PON1 stimulation capacity of rHDL particles.

Main Methods:

• Reconstituted HDL (rHDL) particles were prepared with varying concentrations of Ox-PL.
• Physicochemical properties of the rHDL particles, including lipid domain characteristics, apoA-I conformation, and stability, were analyzed.
• The capacity of modified rHDL particles to stimulate PON1 activity was compared.

Main Results:

• Increased Ox-PL content significantly altered the physicochemical properties of the rHDL lipid domain.
• The stability of rHDL particles decreased, and the conformation and orientation of apoA-I molecules were modified with rising Ox-PL levels.
• A notable decrease in the PON1 stimulation capacity of rHDL particles was observed as Ox-PL content increased.

Conclusions:

• Oxidized phospholipids destabilize the structural integrity of HDL particles.
• The presence of Ox-PLs alters HDL's molecular conformation and function, impacting apoA-I's role.
• These structural and functional modifications of HDL by Ox-PLs contribute to the loss of athero-protective effects and potentially promote pro-atherogenic activities.