# Effects of HDL Structure and Function in Peripheral Artery Disease

## TL;DR

This study explores how the structure and function of HDL, rather than its quantity, influence peripheral artery disease, finding that oxidized HDL increases while certain HDL subfractions decrease in severe cases.

## Contribution

The study identifies specific HDL subfractions and oxidized HDL as key indicators in peripheral artery disease progression.

## Key findings

- Ox-HDL levels significantly increase with disease severity in peripheral artery disease.
- HDL-C, HDL-P, and S-HDL-P levels decrease in severe peripheral artery disease cases.
- Three SNPs show differential associations with HDL subfractions and Ox-HDL levels.

## Abstract

The structure and function of high-density lipoprotein (HDL), rather than its concentration, are more important factors in determining HDL activity. HDL particles (HDL-P) are heterogeneous in their composition, size, and antioxidative function. We investigated the levels of HDL subfractions and oxidized high-density lipoprotein (Ox-HDL) and validated their correlation with genetic determinants underlying peripheral artery disease (PAD). We recruited a PAD population stratified by claudication severity (group I) and critical limb ischemia (group II) according to the Rutherford classification. We found that the level of Ox-HDL was significantly increased with Rutherford classification (group II; p = 0.001). Conversely, the levels of high-density lipoprotein cholesterol (HDL-C), HDL-P, and small high-density lipoprotein particles (S-HDL-P) were significantly reduced in group II. Three single nucleotide polymorphisms (SNPs) were differentially associated with HDL particles and Ox-HDL. Briefly, rs117685211 and rs7934858 showed opposing effects, with rs117685211 and rs148877054 being associated with low levels of HDL subfractions; rs148877054 was significantly associated with M and S-HDL-P. Our study indicated the significance of HDL subfractions and Ox-HDL in the pathogenesis of PAD.