Whereas hormonal therapy (HT) may increase the risk of coronary heart disease (CHD) and stroke in menopausal women, epidemiological studies (protection in premenopausal women) suggest and experimental studies (prevention of fatty streak development in animals) demonstrate a major atheroprotective action of estradiol (E2). The understanding of the deleterious and beneficial effects of estrogens is thus required at both a cellular and molecular level.Both the endothelium and the immuno-inflammatory system 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 rather elicits a pro-inflammatory response in vivo at the level of several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. E2 promotes beneficial actions on the endothelium such as nitric oxide and prostacyclin production.E2 actions are essentially mediated by two molecular targets: estrogen receptor alpha (ER-alpha) and beta (ER-beta), but the former appears to mediate most of the actions of E2 on the endothelium and on the immune system. ER-alpha modulates target gene transcription through two activation functions (AF), AF-1 and AF-2, even though signalling via ER-alpha located at the plasma membrane (responsible for membrane-initiated steroid signalling (MISS)/(extra-genomic)) can also lead to an indirect effect on gene transcription. Recently, we demonstrated that ER-alpha AF-1 is not required for the vasculoprotective actions of E2, whereas it is necessary for the effects of E2 on its reproductive targets. These results suggest that selective estrogen receptor modulators stimulating ER-alpha with minimal activation of ER-alpha AF-1 could retain beneficial vascular actions, while minimizing the sexual effects.

Une des avancées les plus remarquables des dernières années dans le domaine de la biologie vasculaire est la découverte de l'importance des cellules souches en général et des progéniteurs endothéliaux circulants en particulier (PECs). Ces cellules angiogéniques, qui conservent les propriétés des angioblastes embryonnaires, sont des résidents normaux de la moelle osseuse, qui peuvent être présentes dans la circulation générale soit spontanément soit en réponse à différents stimuli (cytokines pro-inflammatoires, facteurs de croissance, ischémie, statines…). Impliquées dans les mécanismes de réparation vasculaire et tissulaire, les PECs apparaissent comme de bons biomarqueurs de sévérité de l'atteinte endothéliale dans les pathologies cardiovasculaires, mais aussi lors d'atteintes respiratoires hypoxémiantes et dans le sepsis. La découverte de ces cellules a également ouvert une voie thérapeutique innovante pour le traitement des maladies cardiovasculaires ischémiques.One of the most important breakthroughs in the field of vascular biology in the last decade was the discovery of endothelial progenitor cells (EPCs). These angiogenic cells are bone marrow residents, and mobilize to the general circulation spontaneously and in response to various stimuli such as ischemia, growth factor, pro-inflammatory cytokines, and drugs such as statins. Evidence is accumulating that EPCs can differentiate into mature endothelial cells and facilitate endothelial repair and angiogenesis in vivo. In recent years, consistent publications have shown that EPCs provide both diagnostic and prognostic informations with respect to cardiovascular diseases, acute lung injury and sepsis. Mobilization of the EPCs from the bonne marrow or injection of these cells may be used as therapeutic option for the treatment of ischaemic cardiovascular diseases.