Modulation of the Expression of Estrogen Receptors for the Prevention or Treatment of Heart Disease

摘要

The present invention relates to the upregulation of estrogen receptors (ER) alpha (ERα) and/or beta (ERβ) in endothelial cells and/or smooth muscle cells to prevent or treat heart disease. The upregulation is achieved through the use of recombinant DNA technology and, depending on therapeutic needs, may be performed with a simultaneous or subsquent downregulation, as with antisense technology. Oligonucleotides coding for ERα and/or ERβ are introduced into the targeted cells through the use of adenoviruses, for example. With an increase in receptors, the cells should be more responsive to such agonists as 17-beta-estradiol (17βE) and related compounds (genistein, estradiol derivatives . . . ) to improve plaque stabilization, vascular healing and endothelial recovery after vascular injury. Such oligonucleotides may be used to modulate the beneficial effects mediated by the ER on vascular healing, for example, restenosis or plaque stabilisation, in mammals. They may further be used in the prevention or treatment of a disease or disorder characterised by atherosclerosis, plaque vulnerability or destabilisation or pathological plaque rupture or erosion including spontaneous or induced injury.