14 research outputs found
Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus
Paradoxical effect of red wine polyphenols, Provinols (TM) fit the regulation of cyclo-oxygenases in vessels front Zucker fatty rats (Fa/Fa)
Paradoxical effect of red wine polyphenols, Provinols (TM) fit the regulation of cyclo-oxygenases in vessels front Zucker fatty rats (Fa/Fa)
Resveratrol Improved Flow-Mediated Outward Arterial Remodeling in Ovariectomized Rats with Hypertrophic Effect at High Dose
COX-2-Derived Prostanoids and Oxidative Stress Additionally Reduce Endothelium-Mediated Relaxation in Old Type 2 Diabetic Rats
Endothelial dysfunction in renal arcuate arteries of obese Zucker rats: The roles of nitric oxide, endothelium-derived hyperpolarizing factors, and calcium-activated K+ channels
Unique Vascular Benefits of Estetrol, a Native Fetal Estrogen with Specific Actions in Tissues (NEST)
peer reviewedEstrogens (E), in combination with oral contraceptives (COCs) and hormone replacement therapy (HRT) drugs used for the relief of climacteric symptoms of menopause, increase the synthesis of clotting factors, decrease the levels of coagulation inhibitors, and increase the risk of venous thromboembolic events (VTE). Ischemic stroke incidence in postmenopausal women during HRT use is also increased and is probably due to a thrombotic event. This suggests that a safer estrogen may reduce stroke and VTE incidence, with lower impact on hemostasis.
Estetrol (E4) is a relatively recently described new human-specific E produced exclusively by the fetal liver during pregnancy. This Native (human and natural) E has Selective actions in Tissues (NEST). Nest activities of E4 are the consequence of its unique dual role. It activates the nuclear estrogen receptor alpha (ERα) but antagonizes the membrane ERα in contrast to other E, which activate both types of receptors. Most beneficial effects of E on the vascular system have been ascribed to the activation of the membrane ERα of vascular endothelial cells, including enhancement of nitric oxide (NO) production, vasodilation, and prevention of atherosclerosis, of neointimal proliferation, and of hypertension. In a series of papers reviewed here, the INSERM team in Toulouse has demonstrated, by the combined use of pharmacological tools and of transgenic mice lacking either the nuclear ERα, the membrane ERα, or both, that the nuclear ERα plays a major role in controlling E activities in vessels. E4 is able to elicit the important vasculoprotective actions mediated by estradiol (E2). Furthermore, phase 1 and 2 clinical studies of E4 in a contraceptive indication (in combination with drospirenone) or in postmenopausal women for the relief of climacteric complaints demonstrate that E4 has a minimal impact on hemostasis, coagulation factors, coagulation inhibitors, fibrinolysis, angiotensinogen, triglycerides, and cholesterol. Altogether, preclinical studies and phase 1 and 2 clinical data indicate that E4 could be a new E with a better safety/efficacy profile than other E for women’s healthcare