Control of apoptosis of cardiovascular fibroblasts: a novel drug target.
Adequate control of survival or programmed cell death (apoptosis) of cardiovascular cells appears as an important drug target. While prevention of apoptotic death of cardiomyocytes has been assessed in detail, selective induction of apoptosis of vascular smooth muscle cells or fibroblasts could also be of relevance. Thus, induction of apoptosis of vascular smooth muscle cells by p65 NF-kappa B and Bcl-xL antisense oligonucleotides or p53 overexpression could be useful for limiting vascular lesions associated with restenosis. Although fibroblasts represent the majority of cardiac cells, few attempts were made to induce fibroblast apoptosis in disorders associated with excessive collagen deposition and fibrosis. It is hypothesized that early interference with fibroblast proliferation after myocardial infarction or inflammatory heart disease limits fibrosis which further impairs cardiac performance. A candidate approach could involve growth factor analogues which are known to induce fibroblast apoptosis when an incomplete growth stimulus persists.
Department of Internal Medicine and Cardiology, Philipps-University of Marburg, Germany. Rupp@mailer.uni-marburg.de
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D000925:Anticoagulants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077214:Becaplermin; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D005355:Fibrosis; D006331:Heart Diseases / Q000473:pathology*; D006801:Humans; D009206:Myocardium / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis
D000925:Anticoagulants; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin