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Estradiol Action in Atherosclerosis and Reendothelialization

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Book cover Tissue-Specific Estrogen Action

Part of the book series: Ernst Schering Foundation Symposium Proceedings ((SCHERING FOUND,volume 2006/1))

Abstract

Whereas hormonal replacement/menopause therapy (HRT) in postmenopausal women increases coronary artery disease risk, epidemiological studies (protection in premenopaused women) suggest and experimental studies (prevention of the development of fatty streaks in animals) demonstrate a major atheroprotective action of estradiol (E2). The understanding of the deleterious and beneficial effects of estrogens is thus required. The atheroprotective effect of E2 is absent in mice deficient in mature T and B lymphocytes, demonstrating the crucial role of the endothelium/immune system pair. The immunoinflammatory system appears to play a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favors an anti-inflammatory effect in vitro (cultured cells), it elicits in vivo a pro-inflammation at the level of several subpopulations of the immunoinflammatory system, which could contribute to plaque destabilization. Endothelium appears to be an important target for E2, since it potentiates endothelial NO and prostacyclin production, thus promoting beneficial effects such as vasorelaxation and inhibition of platelet aggregation. Prostacyclin, but not NO, appear to be involved in the atheroprotective effect of E2, which also accelerates endothelial regrowth, thus favoring vascular healing. Finally, most of these E2 effects are mediated by estrogen receptor α and are independent of estrogen receptor β. In summary, a better understanding of the mechanisms of estrogens on the normal and atheromatous arteries is required and should help to optimize the prevention of cardiovascular disease after menopause. These mouse models should help to screen existing and future selective estrogen receptor modulators (SERMs).

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Acknowledgements

We are grateful to Prof. F. Bayard for his input to our team's work over many years. We are grateful to P. Chambon, A. Krust, K. Korach, J.C. Guery, A.P. Gadeau, C. Filipe, A. Billon, and B. Calippe for helpful discussions over many years. We thank M.J. Fouque and A. Schambourg for their skillful technical assistance. The work described herein was supported in part by Université Paul Sabatier Toulouse III, INSERM, the European Vascular Genomics Network No. 503254, the Fondation de France, the Fondation de l'Avenir, and the Conseil Régional Midi-Pyrénées in France.

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  1. INSERM U589, INSTITUT L. BUGNARD, 1 avenue Jean Poulhès, 31403, Toulouse Cedex, France

    J.- F. Arnal, H. Laurell, F. Lenfant, V. Douin-Echinard, L. Brouchet & P. Gourdy

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  1. J.- F. Arnal
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  2. H. Laurell
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  4. V. Douin-Echinard
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Correspondence to J.- F. Arnal .

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K. S. Korach T. Wintermantel

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Arnal, J.F., Laurell, H., Lenfant, F., Douin-Echinard, V., Brouchet, L., Gourdy, P. (2007). Estradiol Action in Atherosclerosis and Reendothelialization. In: Korach, K.S., Wintermantel, T. (eds) Tissue-Specific Estrogen Action. Ernst Schering Foundation Symposium Proceedings, vol 2006/1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/2789_2006_017

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