Abstract
Sex hormone replacement therapy has been shown to attenuate atherogenesis, although the mechanisms for this effect are incompletely defined. In previous studies, we showed that tumor necrosis factor-α (TNF) increased LDL accumulation in artery walls by superoxide-mediated modification of LDL. Incubation of LDL with 17-β estradiol (E2) significantly attenuated this effect. To more carefully examine the effect of female sex hormones in the artery wall on LDL accumulation under control and oxidant stress (TNF) conditions, we implanted two-month old ovariectomized rats with 21-day release pellets containing either: 0.25mg E2; 2.5mg E2; 50mg progesterone(P); 50mg P+ 0.25mg E2; or placebo. Carotid arteries were removed and perfused under physiological conditions. Using quantitative fluorescence microscopy, rates of fluorescently-labeled LDL accumulation were measured before and after treatment with 10ng/ml TNF. Although no significant differences between treatment groups were observed with these small sample sizes (p<.1), baseline rates of LDL accumulation were low for the 2.5mg E2(n=5) and 0.25mg E2(n=6) treatment groups (0.054±0.016 mV/min and 0.075±0.005 mV/min, respectively) compared to the control(n=5) and E2+ P-implanted (n=6) groups (0.112±0.025mV/min and 0.118±0.040 mV/min, respectively). TNF treatment significantly increased LDL accumulation in all hormone treatment groups(p<.05). In conclusion, E2 treatment tended to decrease baseline LDL accumulation rate in perfused arteries but had no effect on TNF-mediated increases in LDL accumulation. These experiments suggest incorporation of estradiol into the LDL particle may be important in preventing LDL modification and binding in the artery wall.
| Original language | English (US) |
|---|---|
| Journal | FASEB Journal |
| Volume | 11 |
| Issue number | 3 |
| State | Published - 1997 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Cell Biology
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Effects of female sex hormones on LDL accumulation in the artery wall. / Walsh, Barbara A.; Rutledge, John C.
In: FASEB Journal, Vol. 11, No. 3, 1997.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of female sex hormones on LDL accumulation in the artery wall
AU - Walsh, Barbara A.
AU - Rutledge, John C
PY - 1997
Y1 - 1997
N2 - Sex hormone replacement therapy has been shown to attenuate atherogenesis, although the mechanisms for this effect are incompletely defined. In previous studies, we showed that tumor necrosis factor-α (TNF) increased LDL accumulation in artery walls by superoxide-mediated modification of LDL. Incubation of LDL with 17-β estradiol (E2) significantly attenuated this effect. To more carefully examine the effect of female sex hormones in the artery wall on LDL accumulation under control and oxidant stress (TNF) conditions, we implanted two-month old ovariectomized rats with 21-day release pellets containing either: 0.25mg E2; 2.5mg E2; 50mg progesterone(P); 50mg P+ 0.25mg E2; or placebo. Carotid arteries were removed and perfused under physiological conditions. Using quantitative fluorescence microscopy, rates of fluorescently-labeled LDL accumulation were measured before and after treatment with 10ng/ml TNF. Although no significant differences between treatment groups were observed with these small sample sizes (p<.1), baseline rates of LDL accumulation were low for the 2.5mg E2(n=5) and 0.25mg E2(n=6) treatment groups (0.054±0.016 mV/min and 0.075±0.005 mV/min, respectively) compared to the control(n=5) and E2+ P-implanted (n=6) groups (0.112±0.025mV/min and 0.118±0.040 mV/min, respectively). TNF treatment significantly increased LDL accumulation in all hormone treatment groups(p<.05). In conclusion, E2 treatment tended to decrease baseline LDL accumulation rate in perfused arteries but had no effect on TNF-mediated increases in LDL accumulation. These experiments suggest incorporation of estradiol into the LDL particle may be important in preventing LDL modification and binding in the artery wall.
AB - Sex hormone replacement therapy has been shown to attenuate atherogenesis, although the mechanisms for this effect are incompletely defined. In previous studies, we showed that tumor necrosis factor-α (TNF) increased LDL accumulation in artery walls by superoxide-mediated modification of LDL. Incubation of LDL with 17-β estradiol (E2) significantly attenuated this effect. To more carefully examine the effect of female sex hormones in the artery wall on LDL accumulation under control and oxidant stress (TNF) conditions, we implanted two-month old ovariectomized rats with 21-day release pellets containing either: 0.25mg E2; 2.5mg E2; 50mg progesterone(P); 50mg P+ 0.25mg E2; or placebo. Carotid arteries were removed and perfused under physiological conditions. Using quantitative fluorescence microscopy, rates of fluorescently-labeled LDL accumulation were measured before and after treatment with 10ng/ml TNF. Although no significant differences between treatment groups were observed with these small sample sizes (p<.1), baseline rates of LDL accumulation were low for the 2.5mg E2(n=5) and 0.25mg E2(n=6) treatment groups (0.054±0.016 mV/min and 0.075±0.005 mV/min, respectively) compared to the control(n=5) and E2+ P-implanted (n=6) groups (0.112±0.025mV/min and 0.118±0.040 mV/min, respectively). TNF treatment significantly increased LDL accumulation in all hormone treatment groups(p<.05). In conclusion, E2 treatment tended to decrease baseline LDL accumulation rate in perfused arteries but had no effect on TNF-mediated increases in LDL accumulation. These experiments suggest incorporation of estradiol into the LDL particle may be important in preventing LDL modification and binding in the artery wall.
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UR - http://www.scopus.com/inward/citedby.url?scp=26144461201&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:26144461201
VL - 11
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 3
ER -