The IGF-1 Receptor as a Therapeutic Target to Improve Endothelial Progenitor Cell Function
Bone marrow-derived circulating endothelial progenitor cells (EPC) participate in angiogenesis and vascular homeostasis by incorporating into the endothelium of damaged vessels and, perhaps more importantly, exhibiting potent angiogenic paracrine effects ( 1). EPC are embedded in the microenvironment of bone marrow stromal and endothelial cells and translocate to the circulation upon NO-mediated signaling ( 2). Additional mobilizing pathways include extracellular signal-regulated kinases (ERK)/matrix metalloproteinase-9 (MMP-9)-mediated release of soluble c-Kit ligand ( 3). EPC participate in postnatal growth of new blood vessels and/or are home to sites of endothelial damage, maintaining endothelial integrity and function. Circulating EPC numbers are tightly correlated to endothelial function and serve as an independent predictor for cardiovascular diseases ( 4). Functionalproperties of EPC may be of equal or greater importance than quantitative alterations. A variety of functional...
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