The present invention provides novel antisense oligonucleotides that target the genes and mRNAs encoding mammalian Estrogen Receptors (ER) alpha and/or beta and modulate the receptors' responses. These antisense oligonucleotides may be used alone or in combination with 17 Beta estradiol or a related compound (genistein, estradiol derivatives . . . ) to improve plaque stabilization, vascular healing and endothelial recovery after vascular injury. Also provided are methods for designing and testing the antisense oligonucleotides. 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. The present invention further pertains to pharmaceutical compositions and formulations comprising the novel antisense oligonucleotides of the present invention for use in the treatment of mammals having a disease or disorder characterised by atherosclerosis, plaque vulnerability or destabilisation or pathological plaque rupture or erosion including spontaneous or induced injury.