Abstract 1345: Short Term Administration of Reconstituted ApoAI Discs Increases Circulating Progenitor Cells in Type 2 Diabetes
Introduction: Type 2 diabetes (DM2) is associated with reduced endothelial regenerative capacity due to decreased levels of circulating endothelial progenitor cells (EPC) and impaired EPC function. Reduced EPC levels play an important role in the development of atherosclerotic disease. Low concentration of high-density lipoprotein (HDL) cholesterol contributes to the increased risk of cardiovascular disease in DM2. A strong inverse relation exists between HDL levels and cardiovascular risk. Enhancing HDL improved endothelial function in patients with increased cardiovascular risk. We hypothesized that systemic infusion of apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) disks improves progenitor cell availability in patients with DM2.
Methods: Seven patients with uncomplicated DM2 (HDL<1.1 mmol/l) received systemic apoA-I/PC infusion (CSL, Sydney, Australia) during a period of 4 hours at a dose of 80 mg/kg body weight. Peripheral blood samples were obtained before (baseline) and directly after the infusion (t=4) as well as 24 hours and 7 days (t=7d) after infusion of apoA-l/PC. Circulating EPC, defined as VEGFR-2+/CD34+ cells and hematopoietic CD34+ cells, were determined in peripheral blood by flow cytometry. Results: After apoA-I/PC infusion, plasma apoA1 levels increased by 55%. Immediately after infusion CD34+ cell count tended to decrease (baseline 3200±1673 versus t=4 2959±1417 per ml blood, n.s), which was followed by a significant increase at 7 days after infusion (4694±1773 per ml blood, p<0.001). We also observed a tendency towards increased EPC number after 7 days (baseline 480±225 versus t=7d 1060±917 per ml blood, p=0.14).
Conclusion: A single, rapid infusion of apoA-I/PC in patients with DM2 increases the availability of CD34+ hematopoietic cells and EPC. This improvement was seen 7 days after infusion, indicating a long term effect on mobilization of CD34+ cells and EPC. The functional effect of HDL on progenitor cells remains to be elucidated. Further experiments are warranted to discern whether this is a common feature of HDL-increasing strategies, or whether it is restricted to apoAI-infusion.