Abstract
Estrogens have direct effects on the vascular wall that may prevent the development of atherosclerosis. In particular, estrogens, such as 17β- estradiol (estradiol), are known to have potent antioxidant activity. Tumor necrosis factor-α (TNF) is found in human atheroma and produces oxygen- derived free radicals. These oxygen-derived free radicals may modify low density lipoproteins (LDL) and increase LDL binding in the artery wall. We asked: 1) does TNF increase LDL accumulation in the artery wall and 2) can the TNF-mediated increase in LDL accumulation be prevented by the antioxidant activity of estradiol? Carotid arteries from ovariectomized 3-month-old rats were removed and perfused with fluorescently labeled LDL and arterial LDL flux was measured using quantitative fluorescence microscopy. In six arteries, addition of TNF (10 ng/ml) to the perfusate resulted in a 2.3-fold increase in the rate of LDL accumulation (1.50 ± 0.37 ng/min per cm2 vs. 3.38 ± 0.48 ng/min per cm2; P < 0.01). Estradiol (65 pg/ml) and α- tocopherol (6 mg/L) both attenuated TNF-mediated LDL accumulation (P < 0.05), indicating that TNF may exert its effects on LDL accumulation through cellular production of oxygen-derived free radicals. These results support an antioxidant role for estradiol in the protection against LDL accumulation in the artery wall and subsequent progression of atherosclerosis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 387-396 |
| Number of pages | 10 |
| Journal | Journal of Lipid Research |
| Volume | 40 |
| Issue number | 3 |
| State | Published - Mar 1999 |
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Keywords
- Antioxidants
- Atherosclerosis
- Carotid arteries
- Lipoprotein flux
- Sex hormones
ASJC Scopus subject areas
- Endocrinology
Cite this
17β-estradiol reduces tumor necrosis factor-α-mediated LDL accumulation in the artery wall. / Walsh, Barbara A.; Mullick, Adam E.; Walzem, Rosemary L.; Rutledge, John C.
In: Journal of Lipid Research, Vol. 40, No. 3, 03.1999, p. 387-396.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 17β-estradiol reduces tumor necrosis factor-α-mediated LDL accumulation in the artery wall
AU - Walsh, Barbara A.
AU - Mullick, Adam E.
AU - Walzem, Rosemary L.
AU - Rutledge, John C
PY - 1999/3
Y1 - 1999/3
N2 - Estrogens have direct effects on the vascular wall that may prevent the development of atherosclerosis. In particular, estrogens, such as 17β- estradiol (estradiol), are known to have potent antioxidant activity. Tumor necrosis factor-α (TNF) is found in human atheroma and produces oxygen- derived free radicals. These oxygen-derived free radicals may modify low density lipoproteins (LDL) and increase LDL binding in the artery wall. We asked: 1) does TNF increase LDL accumulation in the artery wall and 2) can the TNF-mediated increase in LDL accumulation be prevented by the antioxidant activity of estradiol? Carotid arteries from ovariectomized 3-month-old rats were removed and perfused with fluorescently labeled LDL and arterial LDL flux was measured using quantitative fluorescence microscopy. In six arteries, addition of TNF (10 ng/ml) to the perfusate resulted in a 2.3-fold increase in the rate of LDL accumulation (1.50 ± 0.37 ng/min per cm2 vs. 3.38 ± 0.48 ng/min per cm2; P < 0.01). Estradiol (65 pg/ml) and α- tocopherol (6 mg/L) both attenuated TNF-mediated LDL accumulation (P < 0.05), indicating that TNF may exert its effects on LDL accumulation through cellular production of oxygen-derived free radicals. These results support an antioxidant role for estradiol in the protection against LDL accumulation in the artery wall and subsequent progression of atherosclerosis.
AB - Estrogens have direct effects on the vascular wall that may prevent the development of atherosclerosis. In particular, estrogens, such as 17β- estradiol (estradiol), are known to have potent antioxidant activity. Tumor necrosis factor-α (TNF) is found in human atheroma and produces oxygen- derived free radicals. These oxygen-derived free radicals may modify low density lipoproteins (LDL) and increase LDL binding in the artery wall. We asked: 1) does TNF increase LDL accumulation in the artery wall and 2) can the TNF-mediated increase in LDL accumulation be prevented by the antioxidant activity of estradiol? Carotid arteries from ovariectomized 3-month-old rats were removed and perfused with fluorescently labeled LDL and arterial LDL flux was measured using quantitative fluorescence microscopy. In six arteries, addition of TNF (10 ng/ml) to the perfusate resulted in a 2.3-fold increase in the rate of LDL accumulation (1.50 ± 0.37 ng/min per cm2 vs. 3.38 ± 0.48 ng/min per cm2; P < 0.01). Estradiol (65 pg/ml) and α- tocopherol (6 mg/L) both attenuated TNF-mediated LDL accumulation (P < 0.05), indicating that TNF may exert its effects on LDL accumulation through cellular production of oxygen-derived free radicals. These results support an antioxidant role for estradiol in the protection against LDL accumulation in the artery wall and subsequent progression of atherosclerosis.
KW - Antioxidants
KW - Atherosclerosis
KW - Carotid arteries
KW - Lipoprotein flux
KW - Sex hormones
UR - http://www.scopus.com/inward/record.url?scp=0032587141&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032587141&partnerID=8YFLogxK
M3 - Article
C2 - 10064726
AN - SCOPUS:0032587141
VL - 40
SP - 387
EP - 396
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 3
ER -