HDL-associated estradiol stimulates endothelial NO synthase and vasodilation in an SR-BI–dependent manner
J. Clin. Invest. Ming Gong, et al. 111:1579 doi:10.1172/JCI16777 [
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Figure 1HDL isolated from female subjects stimulates the production of nitric oxide. HDL, LDL, and VLDL were isolated from young, reproductively competent female humans (
a) and mice (
b) and age-matched male humans (
a) and mice (
b) (
31). The freshly isolated lipoproteins (10 μg/ml) were incubated with human microvascular endothelial cells that had been prelabeled with 0.75 μCi/ml of [
3H]arginine for 15 minutes at 37°C (
21). An additional set of cells was treated with 1 μg/ml of ionomycin to determine the maximal eNOS stimulation. The cells were then washed, lysed, and extracted, and radiolabeled arginine was separated from radiolabeled citrulline using an ion-exchange column. Each experiment included controls, using 1 mM
L-NNA to demonstrate that over 99% of the generated citrulline was due to eNOS activity (data not shown). In (
c), a concentration curve of the effect of female HDL on eNOS activity is shown. The data are from six to eight independent experiments, with triplicate measurements in each experiment (mean ± SE).