Atherosclerosis and Vascular Biologic Responses to Estrogens: Histologic, Immunohistochemical, Biochemical, and Molecular Methods

  • Thomas C. Register
  • Susan E. Appt
  • Thomas B. Clarkson
Part of the Methods in Molecular Biology book series (MIMB, volume 1366)


Atherogenesis is a multifactorial pathologic process influenced by genetics and environmental factors such as diet, exercise, stress, and other exposures. Estrogen receptors (ER) are expressed in cells of the arterial wall, suggesting that estrogen receptor ligands (estradiol, natural and pharmacologic ligands) may directly affect arterial biology and atherogenesis. Ligand bound estrogen receptor alpha and beta (ERα, ERβ) can influence physiology through direct binding to estrogen response elements in the DNA, through interactions with other transcription factors such as NF-κB, or through rapid effects not dependent on gene expression changes but instead through non-nuclear membrane sites involving ERα, ERβ, or G-coupled protein ER (GPER1).

Elucidation of potential direct effects of estrogens on the artery wall requires careful evaluation of arterial biologic responses to estrogens. We have developed a comprehensive approach to understand the mechanisms of estrogen action which employs histologic measures of the size and other characteristics of atherosclerotic lesions, immunohistochemical assessments of cellular composition, evaluation of chemical, molecular, and genomic changes in the arterial environment, and determination of the relationships between arterial estrogen receptor expression and atherogenesis. This approach can provide important insights into the mechanisms of action of estrogen and other mediators of atherogenesis.

Key words

Atherosclerosis Inflammation Vascular biology Gene expression Macrophage T cell Estrogenreceptoralpha and beta 


Source of Funding

This project was supported by NIH grants AG18170 (TCR), AG28641 (TCR), and HL45666 (TBC).


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Thomas C. Register
    • 1
  • Susan E. Appt
    • 1
  • Thomas B. Clarkson
    • 1
  1. 1.Department of Pathology, Section on Comparative MedicineWake Forest School of MedicineWinston-SalemUSA

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