NK Cell Mediated Cytotoxicity: A Potential Mechanism of Endothelial Progenitor Cell Dysfunction in the SS Rat

Endothelial progenitor cells (EPCs) are adult stem cells with roles in angiogenesis and endothelial function. Studies suggest that autologous stem cell therapy using EPCs is therapeutic in microvascular disease; however, results from clinical trials have been mixed. EPCs from diseased/aging hosts show decreases in number and function that could compromise their therapeutic efficacy, and this is likely to be masking the potential of EPC based therapy. The objective of this study was to determine the mechanism of EPC dysfunction in an animal model of salt-sensitive hypertension and impaired angiogenesis. In the SS/MCWi (SS) rat, EPC competency and longevity are impaired in vivo but rescued in vitro. We have found that SS EPCs express higher levels of natural killer cell receptor 2B4 (2B4) on their cell membrane than EPCs from healthy genetic controls, consomic SS-13BN rats. 2B4 has been shown to induce NK cell mediated cytotoxicity when overexpressed on target cells. We isolated EPCs and NK cells from SS an...