Control of apoptosis of cardiovascular fibroblasts: A novel drug target

Adequate control of survival or programmed cell death (apoptosis) of cardio vascular cells appears as an important drug target. While prevention of apo ptotic death of cardiomyocytes has been assessed in detail, selective induc tion of apoptosis of vascular smooth muscle cells or fibroblasts could also be of relevance. Thus, induction of apoptosis of vascular smooth muscle ce lls by p65 NF-kappa B and Bcl-x(L) antisense oligonucleotides or p53 overex pression could be useful for limiting vascular lesions associated with rest enosis. Although fibroblasts represent the majority of cardiac cells, few attempts were made to induce fibroblast apoptosis in disorders associated with exces sive collagen deposition and fibrosis. It is hypothesized that early interf erence with fibroblast proliferation after myocardial infarction or inflamm atory heart disease limits fibrosis which further impairs cardiac performan ce. A candidate approach could involve growth factor analogues which are kn own to induce fibroblast apoptosis when an incomplete growth stimulus persi sts.