INHIBITION OF NEOINTIMAL CELL BCL-X EXPRESSION INDUCES APOPTOSIS AND REGRESSION OF VASCULAR-DISEASE

We postulated that activation of a genetic program that tonically inhi bits intimal cell death is a necessary condition for the pathogenesis of vascular disease. Studies of vascular lesions in humans and animal models documented increased expression of the anti-apoptotic gene prod uct Bcl-x(L) within intimal cells. Downregulation of intimal cell bcl- x(L) expression with the use of antisense oligonucleotides induced apo ptosis and acute regression of vascular lesions. These findings indica te that apoptosis regulatory genes such as bcl-x(L) are critical deter minants of intimal lesion formation and that targeted apoptosis may be a novel therapy for intimal vascular disease.