Abstract 5636: Time From Onset of Acute Anterior Myocardial Infarction Negatively Influences Bone Marrow Cell Function: Preliminary Data From the NHLBI CCTRN Ancillary Studies
Bone marrow (BM) contributes to tissue repair in a time dependent fashion. Impaired BM may lead to decreased response to acute myocardial infarction (AMI) but this hypothesis has been examined only from measurements of peripheral blood (PB) cells among heterogeneous patients.
Methods: We investigated the association between BM function and time after AMI in a group of patients (mean age 62 years) with recent, initial anterior STEMI, treated by PCI and drug-eluting stenting plus guideline recommended care who had post reperfusion EF ≤ 45% enrolled in CCTRN TIME and Late-TIME trials. BM and PB harvesting were performed at either ≤ 7 days or 14 –21 days after AMI and also from healthy donors. BM and PB endothelial progenitor cells (EPCs) were analyzed by FACS for cell surface phenotyping and by endothelial colony forming cell (ECFC) proliferation.
Results: Healthy BM generated proliferative ECFC colonies. In contrast, BM from ≤7 day AMI patients showed a trend towards decreased ECFC proliferation and from 14 –21 day AMI patients generated less ECFC colonies (P<0.05) with decreased growth rates (P<0.05). To relate results to EPC mobilization, we quantified EPCs in BM and PB and found no differences in number of EPCs in BM among all groups. However, in 14 –21 day AMI subjects there was a decrease in PB circulating EPCs (P<0.05). Decrease in PB EPCs post-AMI positively correlated with decrease in BM-derived ECFC proliferation (r=0.5515, P=0.0268).
Conclusions: These data are consistent with a time-dependent decrease in EPC proliferative potential after initial anterior reperfused STEMI, suggesting AMI events may preface impaired BM-derived vascular progenitor activity. Another possible explanation for the differences seen is subject differences that guided recruitment into the two studies. These results support the rationale of concentrating angiogenic cells for direct application to sites of myocardial injury.