👤 Maaike Kockx

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. Show less

Patients with schizophrenia show a disproportionally increased risk of cardiovascular disease. Hypertriglyceridemia is prevalent in this population; however, how this relates to levels of remnant cholesterol, triglyceride (TG)-rich lipoprotein (TRL) particle size and composition, TG turnover, and apolipoprotein (apo) and angiopoietin-like protein (ANGPTL) concentrations is unknown. Fasting levels of cholesterol (total [TC], LDL-C, HDL-C, non-HDL-C and remnant cholesterol) and TG were determined in 110 patients diagnosed with schizophrenia, and 46 healthy controls. TRL particle size, concentration and composition, and β-hydroxybutyrate (TG turnover marker) were assessed by NMR. Levels of apoCII, apoCIII, apoE, ANGPTL3, ANGPTL4, and ANGPTL8 were measured by ELISA, and apoCII, apoCIII and apoE were further evaluated in HDL and non-HDL fractions. Patients with schizophrenia had significantly elevated TG, TG:apoB ratio, non-HDL-C, remnant cholesterol, non-HDL-apoCII and non-HDL-apoCIII, and HDL-apoE (all P < 0.05), lower HDL-C and apoA-I (all P < 0.001), and comparable apoB, TC, TC:apoB ratio, LDL-C, β-hydroxybutyrate, ANGPTL3, ANGPTL4 and ANGPTL8 to healthy controls. Patients had a 12.0- and 2.5-fold increase in the concentration of large and medium TRL particles respectively, but similar cholesterol:TG ratio within each particle. Plasma TG, remnant cholesterol, and large and medium TRL particle concentrations correlated strongly with apoCII, apoCIII, and apoE in the non-HDL fraction, and with apoCIII and apoE in the HDL fraction in patients with schizophrenia. Differences in TG, HDL-C, TRL particle concentrations, apoCIII, and apoE persisted after adjustment for conventional risk factors. These results are consistent with impaired TRL lipolysis and clearance in patients with schizophrenia which may be responsive to targeting apoCIII. Show less