17β-Estradiol Reverses Shear Stress-Mediated LDL Modifications

Within arterial bifurcations or branching points, oscillatory shear stress (OSS) induces oxidative stress mainly via the NADPH oxidase system. It is unknown whether 17β-estradiol (E2) can regulate OSS-mediated low density lipoprotein (LDL) modifications. Bovine aortic endothelial cells (BAECs) were pre-treated with E2 at 5 nmol/L, followed by exposure to OSS (0 ± 3.0 dynes/ cm2sec and 60 cycles/min) in a flow system. E2 decreased OSS-mediated NADPH oxidase mRNA expression, and E2-mediated ·NO production was mitigated by the ·NO synthase inhibitor L-NAME. The rates of O2− · production in response to OSS increased steadily as determined by superoxide dismutase-inhibited ferricytochrome c reduction; however, pre-treatment with E2 decreased OSS-mediated O2− · production (n=4, P<0.05). In the presence of native LDL (50 μg/ mL), E2 also significantly reversed OSS-mediated LDL oxidation as determined by high performance liquid chromatography. In the presence of O2− · donor, xanthine oxidase (XO), E2 further reversed XO-induced LDL lipid peroxidation (n=3, P<0.001). Mass spectra were acquired in the m/z 400–1800 range, revealing XO-mediated LDL protein nitration involving tyrosine 2535 in the α-2 domains, whereas pre-treatment with E2 reversed this observation, consistent with th