Browsing by Author "Frias, Miguel"

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    Association between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution
    (2016) Woudberg, Nicholas J; Goedecke, Julia H; Blackhurst, Dee; Frias, Miguel; James, Richard; Opie, Lionel H; Lecour, Sandrine
    Abstract Background Obesity and low high-density lipoprotein-cholesterol (HDL-C) levels are associated with cardiovascular risk. Surprisingly, despite a greater prevalence of obesity and lower HDL concentrations than white women, black South African women are relatively protected against ischaemic heart disease. Methods We investigated whether this apparent discrepancy may be related to different HDL function and subclass distribution in black and white, normal-weight and obese South African women (n = 40). HDL functionality was assessed by measuring paraoxonase (PON) activity, platelet activating factor acetylhydrolase (PAF-AH) activity, Oxygen Radical Absorbance Capacity (ORAC) and quantification of the expression of vascular cell adhesion molecule in endothelial cells. PON-1 and PAF-AH expression was determined in isolated HDL and serum using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. Results PON activity was lower in white compared to black women (0.49 ± 0.09 U/L vs 0.78 ± 0.10 U/L, p < 0.05), regardless of PON-1 protein levels. Obese black women had lower PAF-AH activity (9.34 ± 1.15 U/L vs 13.89 ± 1.21 U/L, p <0.05) and HDL-associated PAF-AH expression compared to obese white women. Compared to normal-weight women, obese women had lower large HDL, greater intermediate and small HDL; an effect that was more pronounced in white women than black women. There were no differences in antioxidant capacity or anti-inflammatory function across groups. Conclusions Our data show that both obesity and ethnicity are associated with differences in HDL functionality, while obesity was associated with decreases in large HDL subclass distribution. Measuring HDL functionality and subclass may, therefore, be important factors to consider when assessing cardiovascular risk.
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    Understanding the relationship between high-density lipoprotein (HDL) subclass distribution and functionality in patients at risk of cardiovascular disease
    (2017) Woudberg, Nicholas; Lecour, Sandrine; Goedecke, Julia H; Frias, Miguel
    Background: Risk factors for cardiovascular disease (CVD) include obesity, ethnicity and hypertension. High-density lipoprotein (HDL) has traditionally served as a marker for CVD risk. Latest studies, however, propose that the composition and subclass distribution and the anti-atherogenic function of HDL are more accurate predictors of CVD risk. We therefore explored whether obesity, ethnicity, exercise and hypertension may modulate HDL composition, subclass and function in three different sample populations of patients affected with these CVD risk factors. Methods: The first study sample population consisted of black and white obese and normal-weight South African women (n=40). In the second sample population, obese black South African women were randomly assigned to exercise (combined aerobic and resistance exercise 4 times/week) or control (sedentary) conditions for 12-weeks (n=32). The third sample population included Nigerian out-patients, divided into healthy controls, hypertensive patients and hypertensive patients with heart failure (HF) (n=80). HDL composition measurements included apolipoproteins A1 and M (ApoA1 and ApoM), paraoxonase (PON1) and platelet activating factor acetylhydrolase (PAF-AH) expression (using Western blotting) and sphingosine-1-phosphate (S1P) content (using mass spectometry). Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. HDL functionality was assessed by measuring PON1 activity, PAF-AH activity, reverse cholesterol efflux capacity, HDL-mediated activation of endothelial nitric oxide synthase (eNOS) and quantification of the expression of vascular cell adhesion molecule in endothelial cells. Results: In all sample populations, HDL-cholesterol concentration was not different between groups. PON1 activity was lower in white compared to black women (0.49±0.09 U/L vs 0.78±0.10 U/L, p<0.05). Obese black women had lower PAF-AH activity compared to obese white women (9.34±1.15 U/L vs 13.89±1.21 U/L, p<0.05). Compared to normal-weight women, obese women had lower large HDL, greater intermediate and small HDL. Compared to the sedentary control condition, exercise training was associated with a decrease in PON1 activity (-8.7±2.4% vs +1.1±3.0%, p<0.05), PAF-AH serum expression (-22.1±8.0% vs +16.9±9.8, p<0.005) and small HDL subclasses (-10.1±5.4% vs +15.7±6.6%, p<0.005). S1P content in HDL was lower in hypertensive and HF patients compared to controls (165 ± 55 vs 201 ± 73 pmol/mg, p < 0.05). HDL subclass distribution was different in hypertensive and HF patients with lower large HDL (48 ± 15 vs 63 ± 7%, p<0.005), higher intermediate (45 ± 7 vs 34 ± 5%, p<0.005) and small HDL (7 ± 9 vs 2 ± 4%, p<0.05). In contrast to HDL from control patients, HDL from all hypertensive patients failed to activate eNOS. Conclusions: In all three sample populations, there were associations between CVD risk factors and measures of HDL quality. HDL subclass distribution differences were associated with obesity and hypertensive heart failure, both in cross-sectional studies and in an exercise intervention study. In African sample populations, consideration of HDL quality rather than total HDL quantity may be a more sensitive marker to assess CVD risk.