Spotlight on endothelial progenitor cell inhibitors: short review.
Endothelial progenitor cells (EPCs) are bone-marrow-derived cells that enter the systemic circulation to replace defective or injured mature endothelial cells. EPCs also contribute to neovascularization and limit the progression of atherosclerosis. Patients with reduced EPC levels or dysfunctional EPCs are at increased risk for coronary artery disease. Drug-mediated improvement of the mobilization, differentiation, function and homing of EPCs to sites of ischemia or injured endothelium may therefore be a promising novel therapeutic approach for various cardiovascular diseases. On the other hand, endogenous inhibitors of EPCs could also be valuable drug targets. The identification of EPC inhibitors and the development of novel drugs that can efficiently regulate production or elimination of these molecules may also be a promising approach for the future treatment of atherosclerosis. In the present review we summarize potential endogenous and exogenous inhibitors of EPCs, such as oxidized low-density lipoproteins, angiotensin II, glucose, cigarette smoke and others. Whenever possible, we also describe the underlying molecular events. Drug-induced mobilization and improvement of EPC function, as well as reduction of EPC inhibitors, is likely to enhance endothelial function and reduce atherosclerotic processes.
Thum
Thomas
T
Medizinische Klinik, Kardiologie, Julius-Maximilians-Universität Würzburg, Germany. Thum_t@klinik.uni-wuerzburg.de
Bauersachs
Johann
J
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D050197:Atherosclerosis / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D000804:Angiotensin II; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine