Abstract 4717: Mobilization of Vascular Progenitor Cells in Patients Undergoing PCI Who Are Randomized to Receive Atorvastatin: Serial Assessment and Delineation of Timeline
Objective: Statin therapy at the time of experimental arterial injury mobilizes vascular progenitor cells. Recently we published important data regarding the involvement of blood-borne cells in the early response to arterial injury/stent implantation [PLoS 2008, Card Res 2009]. To date, prospective, blinded data on statin-induced mobilization of vascular progenitor cells does not exist for humans. Thus we tested the hypothesis that Atorvastatin therapy at time of percutaneous coronary intervention (PCI) with stent placement may mobilize vascular progenitor cell populations that are capable of enhancing arterial repair/re-endothelialization.
Methods and Results: Statin naïve male patients undergoing PCI were randomized to placebo (n=10) or treatment with Atorvastatin 80 mg (n=10) beginning with a 3 day run-in period prior to PCI. Blood samples were drawn at baseline, immediately pre-procedure and post PCI (4 hours, 24 hours, and 14 days). EPC mobilization was determined by
flow cytometry to enumerate the CD45−, 34+, 133+, 117+ EPC phenotype and
in vitro EPC culture assay.
Atorvastatin therapy resulted in a robust reduction in LDL cholesterol at 14 day follow up (3.0 mmol +/− 0.3 vs 1.4 +/− 0.3, p<0.001) with no effects on CRP levels or the ESR. As measured by flow cytometry, EPC levels were already elevated 2-fold in the Atorvastatin group pre-procedure and remained higher at the 4 and 24 hour time points (p<0.05) but not at 14 days. The in vitro culture assay showed a 1.5–3 fold increase in EPC levels with Atorvastatin compared to control at both the pre- and peri-procedural time periods - an effect that persisted to 14 days (p<0.05). In vitro Atorvastatin failed to alter EPC adhesion, migration or survival.
Conclusions: Atorvastatin therapy initiated 3 days prior to PCI in males results in mobilization of a population of vascular progenitor cells. Transient augmentation of this EPC population by Atorvastatin may be particularly beneficial in promoting early re-endothelialization of stented arterial segments and thereby reduce the theoretical need for ultimate platelet inhibition in order to prevent acute/subacute stent thrombosis. Future studies examining the effects of peri-procedural re-bolusing with Atorvastatin at time of PCI may be warranted.