Endothelial progenitor cell dysfunction: mechanisms and therapeutic approaches

Endothelial progenitor cells (EPC) are a circulating cell population participating in angiogenesis and vascular homeostasis. These cells are of fundamental importance as (re)vascularization is essential for the survival of growing, injured or ischaemic tissues. Indeed, bone-marrowas well as non-bone-marrow-derived EPC contribute to formation of new blood vessels [1,2]. Quantitative assessment of progenitor cells in various cardiovascular diseases revealed altered EPC levels after myocardial infarction, in stable or unstable coronary artery disease (CAD), and heart failure [3–7]. In general, EPC numbers seem to be decreased in many chronic diseases, whereas acute events may transiently increase EPC levels. EPC numbers also have prognostic importance: patients with reduced EPC levels are at increased risk for cardiovascular events and death [8,9], and circulating EPC correlate with enhanced coronary collateral development [10]. However, functional properties of EPC may be of equal or probably greater importance than quantitative alterations. Functional limitations of progenitor cells from patients with CAD were first shown in 2004 [11]. Consequently, treatment of CAD patients after myocardial infarction with autologous (dysfunctional) progenitor cells to improve neovascularization and heart function may be ineffective. Identification of the mechanisms underlying EPC dysfunction in various diseases and patient populations as well as developing treatments for dysfunctional EPC will remain important tasks in future cardiovascular medicine. Insulin-like growth factor 1 corrects age-related decline in EPC number and function