Correlation between circulating endothelial progenitor cell function and allograft rejection in heart transplant patients

Chethan J. Sathya, Rohit Sheshgiri, Jessica Prodger, Laura Tumiati, Diego Delgado, Heather J. Ross, Vivek Rao

Research output: Contribution to journalArticlepeer-review

Abstract

Endothelial progenitor cells (EPCs) may contribute to rejection and cardiac allograft vasculopathy (CAV) by being intrinsically involved in the rejection process and causing neointimal hyperplasia. The mammalian target of rapamycin inhibitors (mTORi), sirolimus and everolimus, have been demonstrated to attenuate the progression of CAV and are cytotoxic to EPC. Thus, one mechanism by which mTORi may protect against CAV is by altering EPC function. Our study measured circulating EPC function and correlated this assessment with rejection episodes in heart transplant (HT) recipients. In addition, we examined the effect of mTORi on EPCs. Patients who received HT at our institution between 1995 and 2007 were included and stratified by International Society for Heart and Lung Transplantation (ISHLT) rejection grade. Group A (n = 13) consisted of patients with at least one moderate/severe rejection episode (grade ≥ 2). Group B (n = 28) patients had no moderate/severe episodes (grade < 2). Patients were also independently stratified based on exposure as mTORi (n = 21) vs. non mTORi (n = 20). To assess EPC functional capacity, we counted the number of colony-forming units (CFU) of EPCs in peripheral blood samples from HT recipients. There were no significant differences in baseline characteristics between groups. The mean EPC-CFU counts/plate for group A (rejecting) were 30 ± 6 vs.16 ± 3 for group B (nonrejecting) (P = 0.03). The EPC-CFU counts/plate in the mTORi group (15 ± 3) were lower compared to the non mTORi (27 ± 5) group (P = 0.04). We found that EPC colony-forming capacity was higher in HT patients who experienced moderate/severe rejection episodes. Patients on mTORi showed a reduced EPC colony count consistent with our previous findings of EPC cytotoxicity. Detection of circulating EPC function post-transplant may reliably identify patient risk level for subsequent allograft rejection and allow for appropriate adjustments to immunosuppression. Converting to mTORi therapy may reduce EPC function and provide a novel mechanism to prevent rejection and possibly attenuate the development of CAV.

Original languageEnglish (US)
Pages (from-to)641-648
Number of pages8
JournalTransplant International
Volume23
Issue number6
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

Keywords

  • Cardiac allograft vasculopathy
  • Endothelial progenitor cell
  • Heart transplantation
  • Rejection
  • Sirolimus

ASJC Scopus subject areas

  • Transplantation

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