Effects of HDL Structure and Function in Peripheral Artery Disease

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.