Endothelial Progenitor Cell Mobilization and Increased Intravascular Nitric Oxide in Patients Undergoing Cardiac Rehabilitation

Abstract

In Brief PURPOSE: We investigated whether cardiac rehabilitation participation increases circulating endothelial progenitor cells (EPCs) and benefits vasculature in patients already on stable therapy previously shown to augment EPCs and improve endothelial function. METHODS: Forty-six of 50 patients with coronary artery disease completed a 36-session cardiac rehabilitation program: 45 were treated with HMG-CoA reductase inhibitor (statin) therapy ≥1 month (average baseline low-density lipoprotein cholesterol = 81 mg/dL). Mononuclear cells isolated from blood were quantified for EPCs by flow cytometry (CD133+/VEGFR-2+ cells) and assayed in culture for EPC colony-forming units (CFUs). In 23 patients, EPCs were stained for annexin-V as a marker of apoptosis, and nitrite was measured in blood as an indicator of intravascular nitric oxide. RESULTS: Endothelial progenitor cells increased from 35 ± 5 to 63 ± 10 cells/mL, and EPC-CFUs increased from 0.9 ± 0.2 to 3.1 ± 0.6 per well (both P < .01), but 11 patients had no increase in either measure. Those patients whose EPCs increased from baseline showed significant increases in nitrite and reduction in annexin-V staining (both P < .01) versus no change in patients without increase in EPCs. Over the course of the program, EPCs increased prior to increase in nitrite in the blood. CONCLUSIONS: Cardiac rehabilitation in patients receiving stable statin therapy and with low-density lipoprotein cholesterol at goal increases EPC number, EPC survival, and endothelial differentiation potential, associated with increased nitric oxide in the blood. Although this response was observed in most patients, a significant minority showed neither EPC mobilization nor increased nitric oxide in the blood. Of 46 coronary artery disease patients who completed a 36-session cardiac rehabilitation program, 35 showed significant increases in circulating endothelial progenitor cells (EPCs). Those patients whose EPCs increased from baseline showed significant increases in nitric oxide in the blood, versus no change in patients without increase in EPCs. Over the course of cardiac rehabilitation, EPCs increased prior to increase in nitric oxide in the blood, consistent with endothelial repair.