TY - JOUR
T1 - High-density lipoprotein cholesterol efflux, nitration of apolipoprotein A-I, and endothelial function in obese women
AU - Vazquez, Edward
AU - Sethi, Amar A.
AU - Freeman, Lita
AU - Zalos, Gloria
AU - Chaudhry, Hira
AU - Haser, Erin
AU - Aicher, Brittany O.
AU - Aponte, Angel
AU - Gucek, Marjan
AU - Kato, Gregory J.
AU - Waclawiw, Myron A.
AU - Remaley, Alan T.
AU - Cannon, Richard O.
PY - 2012/2/15
Y1 - 2012/2/15
N2 - Subjects at risk of atherosclerosis might have dysfunctional high-density lipoprotein (HDL) despite normal cholesterol content in the plasma. We considered whether the efflux of excess cellular cholesterol to HDL from obese subjects is associated with impaired arterial endothelial function, a biomarker of cardiovascular risk. A total of 54 overweight (body mass index [BMI] 25 to 29.9 kg/m 2) or obese (BMI <30 kg/m 2) women, aged 46 ± 11 years, were enrolled in a worksite wellness program. The HDL cholesterol averaged 57 ± 17 mg/dl and was inversely associated with the BMI (r = -0.419, p = 0.002). Endothelial function was assessed using brachial artery flow-mediated dilation. Cholesterol efflux from 3H- cholesterollabeled baby hamster kidney cells transfected with the adenosine triphosphate-binding cassette transporter 1 showed 8.2% to 22.5% cholesterol efflux within 18 hours when incubated with 1% serum and was positively correlated with brachial artery flow-mediated dilation (p <0.05), especially in the 34 subjects with BMI <30 kg/m 2 (r = 0.482, p = 0.004). This relation was independent of age, HDL or low-density lipoprotein cholesterol concentrations in plasma, blood pressure, or insulin resistance on stepwise multiple regression analysis (β = 0.31, R 2 = 0.21, p = 0.007). Nitration of apolipoprotein A-I tyrosine residues (using sandwich enzyme-linked immunosorbent assay) was significantly greater in women with a BMI <30 kg/m 2 and the lowest cholesterol efflux than in women with a BMI of 25 to 29.9 kg/m 2 and the greatest cholesterol efflux (p = 0.01). In conclusion, we have shown that decreased cholesterol efflux by way of the adenosine triphosphate-binding cassette transporter 1 is associated with increased nitration of apolipoprotein A-I in HDL and is an independent predictor of impaired endothelial function in women with a BMI of <30 kg/m 2. This finding suggests that the functional measures of HDL might be better markers for cardiovascular risk than the HDL cholesterol levels in this population.
AB - Subjects at risk of atherosclerosis might have dysfunctional high-density lipoprotein (HDL) despite normal cholesterol content in the plasma. We considered whether the efflux of excess cellular cholesterol to HDL from obese subjects is associated with impaired arterial endothelial function, a biomarker of cardiovascular risk. A total of 54 overweight (body mass index [BMI] 25 to 29.9 kg/m 2) or obese (BMI <30 kg/m 2) women, aged 46 ± 11 years, were enrolled in a worksite wellness program. The HDL cholesterol averaged 57 ± 17 mg/dl and was inversely associated with the BMI (r = -0.419, p = 0.002). Endothelial function was assessed using brachial artery flow-mediated dilation. Cholesterol efflux from 3H- cholesterollabeled baby hamster kidney cells transfected with the adenosine triphosphate-binding cassette transporter 1 showed 8.2% to 22.5% cholesterol efflux within 18 hours when incubated with 1% serum and was positively correlated with brachial artery flow-mediated dilation (p <0.05), especially in the 34 subjects with BMI <30 kg/m 2 (r = 0.482, p = 0.004). This relation was independent of age, HDL or low-density lipoprotein cholesterol concentrations in plasma, blood pressure, or insulin resistance on stepwise multiple regression analysis (β = 0.31, R 2 = 0.21, p = 0.007). Nitration of apolipoprotein A-I tyrosine residues (using sandwich enzyme-linked immunosorbent assay) was significantly greater in women with a BMI <30 kg/m 2 and the lowest cholesterol efflux than in women with a BMI of 25 to 29.9 kg/m 2 and the greatest cholesterol efflux (p = 0.01). In conclusion, we have shown that decreased cholesterol efflux by way of the adenosine triphosphate-binding cassette transporter 1 is associated with increased nitration of apolipoprotein A-I in HDL and is an independent predictor of impaired endothelial function in women with a BMI of <30 kg/m 2. This finding suggests that the functional measures of HDL might be better markers for cardiovascular risk than the HDL cholesterol levels in this population.
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U2 - 10.1016/j.amjcard.2011.10.008
DO - 10.1016/j.amjcard.2011.10.008
M3 - Article
C2 - 22105786
AN - SCOPUS:84856493027
SN - 0002-9149
VL - 109
SP - 527
EP - 532
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - 4
ER -