Acute-phase HDL in phospholipid transfer protein (PLTP)-mediated HDL conversion

Area of Science:

• Biochemistry
• Lipid Metabolism
• Cardiovascular Research

Background:

• Plasma phospholipid transfer protein (PLTP) modifies high-density lipoprotein (HDL) particles.
• During the acute-phase reaction (APR), serum amyloid A (SAA) replaces apo A-I on HDL, potentially altering its function.
• HDL remodeling during APR may impair cholesterol efflux and affect lipid transfer protein substrates.

Purpose of the Study:

• To investigate the properties of SAA-containing HDL during PLTP-mediated conversion.
• To determine if AP-HDL's substrate properties for PLTP are altered by SAA enrichment.

Main Methods:

• Enrichment of HDL with SAA in vitro and in vivo (32-58% SAA content).
• Incubation of SAA-enriched HDL (AP-HDL) with PLTP.
• Analysis of conversion products for size, composition, gel mobility, and apo A-I degradation.

Main Results:

• PLTP facilitated AP-HDL conversion more effectively than native HDL(3), generating large fusion particles (10.5-13.8 nm).
• PLTP released prebeta-HDL from AP-HDL more efficiently than from native HDL(3).
• Prebeta-HDL from AP-HDL contained fragmented apo A-I (approx. 23 kDa); PLTP-mediated apo A-I degradation was more pronounced in AP-HDL.

Conclusions:

• PLTP-mediated conversion of AP-HDL is functional, indicating that prebeta-HDL production remains active during the APR.
• Enhanced PLTP-mediated apo A-I degradation in AP-HDL may contribute to faster catabolism of inflammatory HDL.
• Findings suggest that HDL remodeling during inflammation does not abolish PLTP's role in generating prebeta-HDL subpopulations.