17β-estradiol acts separately on the LDL particle and artery wall to reduce LDL accumulation

Barbara A. Walsh, Adam E. Mullick, Carole E. Banka, John C Rutledge

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Estrogen replacement therapy has been shown to attenuate atherogenesis, although the mechanisms for this effect are incompletely defined. Previously, we showed that 17-β estradiol (estradiol) attenuated oxidant stress-induced increases in vascular low density lipoprotein (LDL) accumulation. It was unclear whether estradiol's effect was imparted on the lipoprotein particle or the artery wall. To examine this, we chronically treated rats with the following sex hormones: low estradiol, high estradiol, progesterone, low estradiol + progesterone, placebo, or control. Carotid arteries (n = 8/group) were isolated and perfused with fluorescently labeled LDL. Rates of LDL accumulation were measured before and after treatment with 10 ng/ml tumor necrosis factor-α (TNF) using quantitative fluorescence microscopy. We observed a 50% decrease in basal LDL accumulation rates (P < 0.01) and a 25% decrease in endothelial layer permeability (P < 0.01) in arteries from estradiol-treated animals. There was no effect of hormone replacement on rate of TNF-induced LDL accumulation (P = 0.451), while incubation of LDL with 65 pg/ml estradiol attenuated the TNF effect (P < 0.01). These experiments suggest two independent mechanisms of anti-atherogenic protection by estradiol: 1) decreased endothelial layer permeability; and 2) incorporation of estradiol into the LDL particle and prevention of LDL binding to the artery wall.

Original languageEnglish (US)
Pages (from-to)134-141
Number of pages8
JournalJournal of Lipid Research
Volume41
Issue number1
StatePublished - Jan 2000

Fingerprint

LDL Lipoproteins
Estradiol
Arteries
Tumor Necrosis Factor-alpha
Progesterone
Permeability
Estrogen Replacement Therapy
Fluorescence microscopy
Gonadal Steroid Hormones
Carotid Arteries
Fluorescence Microscopy
Oxidants
Lipoproteins
Blood Vessels
Rats
Atherosclerosis
Estrogens
Animals
Placebos
Hormones

Keywords

  • Andoxidant
  • Atherosclerosis
  • Carotid arterics
  • Estradiol
  • Lipoprotein flux

ASJC Scopus subject areas

  • Endocrinology

Cite this

17β-estradiol acts separately on the LDL particle and artery wall to reduce LDL accumulation. / Walsh, Barbara A.; Mullick, Adam E.; Banka, Carole E.; Rutledge, John C.

In: Journal of Lipid Research, Vol. 41, No. 1, 01.2000, p. 134-141.

Research output: Contribution to journalArticle

Walsh, Barbara A. ; Mullick, Adam E. ; Banka, Carole E. ; Rutledge, John C. / 17β-estradiol acts separately on the LDL particle and artery wall to reduce LDL accumulation. In: Journal of Lipid Research. 2000 ; Vol. 41, No. 1. pp. 134-141.
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