17beta-Estradiol reverses shear-stress-mediated low density lipoprotein modifications.
Within arterial bifurcations or branching points, oscillatory shear stress (OSS) induces oxidative stress mainly via the reduced nicotinamide adenine dinucleodtide phosphate (NADPH) oxidase system. It is unknown whether 17beta-estradiol (E(2)) can regulate OSS-mediated low-density lipoprotein (LDL) modifications. Bovine aortic endothelial cells were pretreated with E(2) at 5 nmol/L, followed by exposure to OSS (0 +/- 3.0 dynes/cm(2) s and 60 cycles/min) in a flow system. E(2) decreased OSS-mediated NADPH oxidase mRNA expression, and E(2)-mediated (.-)NO production was mitigated by the NO synthase inhibitor N(G)-nitro-l-argenine methyl ester. The rates of O(2)(-.) production in response to OSS increased steadily as determined by superoxide-dismutase-inhibited ferricytochrome c reduction; whereas, pretreatment with E(2) decreased OSS-mediated O(2)(-.) production (n = 4, p < 0.05). In the presence of native LDL (50 microg/mL), E(2) also significantly reversed OSS-mediated LDL oxidation as determined by high-performance liquid chromatography. In the presence of O(2)(-.) donor, xanthine oxidase (XO), E(2) further reversed XO-induced LDL lipid peroxidation (n = 3, p < 0.001). Mass spectra acquired in the m/z 400-1800 range, revealed XO-mediated LDL protein nitration involving tyrosine 2535 in the alpha-2 domains, whereas pretreatment with E(2) reversed nitration, as supported by the changes in nitrotyrosine intensities. Thus, E(2) plays an indirect antioxidative role. In addition to upregulation of endothelial (.-)NO synthase and downregulation of Nox4 expression, E(2) influences LDL modifications via lipid peroxidation and protein nitration.
Hwang
Juliana
J
Department of Biomedical Engineering and Cardiovascular Medicine, Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA 90081, USA.
Rouhanizadeh
Mahsa
M
Hamilton
Ryan T
RT
Lin
Tiantian C
TC
Eiserich
Jason P
JP
Hodis
Howard N
HN
Hsiai
Tzung K
TK
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004958:Estradiol / Q000737:chemistry*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D019255:NADPH Oxidases / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D004958:Estradiol; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases