Effects of HDL Structure and Function in Peripheral Artery Disease

Area of Science:

• Cardiovascular Research
• Lipid Metabolism
• Genetics

Background:

• High-density lipoprotein (HDL) particle structure and function are critical for its activity, more so than concentration.
• HDL particles (HDL-P) exhibit heterogeneity in composition, size, and antioxidant function.
• Peripheral artery disease (PAD) is a complex condition influenced by various factors, including lipid profiles.

Purpose of the Study:

• To investigate the association between HDL subfractions, oxidized high-density lipoprotein (Ox-HDL), and genetic determinants in patients with PAD.
• To correlate the levels of HDL subfractions and Ox-HDL with PAD severity, classified by the Rutherford scale.
• To identify specific single nucleotide polymorphisms (SNPs) associated with altered HDL profiles in PAD.

Main Methods:

• Recruitment of PAD patients stratified into groups based on Rutherford classification (claudication severity and critical limb ischemia).
• Quantification of HDL subfractions, including HDL particles (HDL-P) and small high-density lipoprotein particles (S-HDL-P), and oxidized high-density lipoprotein (Ox-HDL).
• Analysis of genetic associations using single nucleotide polymorphisms (SNPs) related to HDL metabolism and Ox-HDL levels.

Main Results:

• Oxidized high-density lipoprotein (Ox-HDL) levels were significantly elevated in patients with critical limb ischemia (Rutherford group II).
• Levels of HDL particles (HDL-P), HDL cholesterol (HDL-C), and small HDL particles (S-HDL-P) were significantly reduced in Rutherford group II.
• Three SNPs (rs117685211, rs7934858, rs148877054) showed differential associations with HDL particles and Ox-HDL, with specific SNPs linked to reduced HDL subfractions.

Conclusions:

• HDL subfractions and Ox-HDL levels are significantly altered in patients with peripheral artery disease (PAD).
• The findings highlight the importance of HDL structure and oxidation status, rather than just concentration, in PAD pathogenesis.
• Specific genetic variants may influence HDL particle composition and oxidation, contributing to PAD development.