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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause

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Selective agonists of estrogen receptor isoforms: new perspectives for cardiovascular disease

Chiara Bolego1, Elisabetta Vegeto, Christian Pinna

  • 1Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, I-20133 Milan, Italy.

Arteriosclerosis, Thrombosis, and Vascular Biology
|August 19, 2006
PubMed

Insights

Selective estrogen receptor modulators (SERMs) offer potential cardiovascular benefits. Developing isoform-selective ER ligands (I-SERMs) may improve treatment by targeting specific estrogen receptor pathways in the vasculature.

Area of Science:

  • Cardiovascular Science
  • Endocrinology
  • Pharmacology

Background:

  • Estrogen receptors (ERs) play a role in cardiovascular health, but clinical trials with estrogens have yielded mixed results.
  • Poor ER isoform selectivity and tissue specificity of estrogens, along with suboptimal treatment strategies, may explain trial failures.
  • Tissue-selective ER modulators (SERMs) are being explored as safer alternatives to estrogens for cardiovascular disease.

Purpose of the Study:

  • To review the current understanding and strategies for selective ER modulation in the cardiovascular system.
  • To highlight the need for isoform-selective ER ligands (I-SERMs) for improved pharmacological control of ERs.
  • To discuss the potential of combining SERM and I-SERM properties in novel ER ligands targeting the vascular wall.

Main Methods:

  • Literature review of studies on estrogen receptors and cardiovascular effects.
  • Analysis of clinical trial data concerning estrogen and SERM efficacy.
  • Examination of emerging evidence on vascular ER alpha activation.

Main Results:

  • ER-deficient mice models have advanced understanding of estrogen's cardiovascular mechanisms.
  • SERMs show promise as safer cardiovascular agents than endogenous estrogens.
  • Development of I-SERMs is crucial for precise pharmacological control of ERs, particularly for vascular ER alpha.

Conclusions:

  • Targeted modulation of estrogen receptors offers a promising avenue for cardiovascular disease treatment.
  • Future research should focus on developing novel ER ligands with combined SERM and I-SERM characteristics.
  • Vascular-specific ER ligands could lead to improved therapeutic strategies for cardiovascular health.

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