HDL remodeling and enrichment with apoCIII and apoE in Indigenous Australians

Indigenous Australians have an increased risk of type 2 diabetes mellitus (T2DM) and premature cardiovascular disease. Subpopulations of high-density lipoprotein (HDL) have been associated with increased cardiovascular risk, but HDL composition, size, or function have not been studied in Indigenous Australians.

The study consisted of 86 non-Indigenous participants, 43 of whom had T2DM, and 75 Indigenous participants, 36 of whom had T2DM. HDL lipid and apolipoprotein content were determined using enzymatic assays and enzyme-linked immunosorbent assays, respectively, and HDL size and distribution were investigated using nuclear magnetic resonance spectroscopy. Transporter-independent, ATP-binding cassette transporter (ABC)A1- and ABCG1-specific cholesterol efflux capacity (CEC) were determined using cell lines stably expressing human ABCA1 or ABCG1.

Indigenous participants had significantly lower concentrations of large (10.3-12.0 nm), small (7.4-7.8 nm), and total HDL particles, which persisted after adjustment for serum triglyceride (TG), body mass index (BMI), and T2DM. HDL from Indigenous Australians was also highly enriched in TG, apolipoprotein (apo) E, and apoCIII (all P < .001). Transporter-independent and ABCG1-mediated CEC were not different between the populations. ABCA1-specific CEC per HDL particle was higher in Indigenous than in non-Indigenous subjects (P < .001), and persisted after adjustment for TG, BMI, and T2DM. Multivariable analysis identified that ABCA1-specific CEC was independently and positively associated with HDL-apoCIII and HDL-apoE levels.

Indigenous Australians demonstrate significant compositional, size, and functional changes in circulating HDL, which is only partially explained by BMI, hypertriglyceridemia, or T2DM. Remodeled HDL may serve as a biomarker of increased cardiovascular risk in Indigenous Australians.