Dysfunctional Endothelial Progenitor Cells in Patients with Hodgkin’s Lymphoma in Complete Remission - The 66th Annual Conference of the Israel Heart Society & The Israel Society of Cardiothoracic Surgery

Maya Wiessman ^1,5 Dorit Leshem ^2,5 Moshe Yeshurun ^3,5 Hagai Yavin ^4,5 Zaza Iakobishvilli ⁵ Pia Raanani ^3,5 Ran Kornowski ^4,5 Eli I. Lev ^6,7 Mordehay Vaturi ^4,5

¹Medicine D, Beilinson Hospital, Rabin Medical Center
²Felsenstein Research Institute, Beilinson Hospital, Rabin Medical Center
³Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center
⁴Department of Cardiology, Rabin Medical Center
⁵Sackler Faculty of Medicine, Tel Aviv University
⁶Department of Cardiology, Assuta ‘Samson’ Ashdod Medical Center
⁷Faculty of Health Sciences, Ben Gurion University of the Negev

Background: The level and function of circulating endothelial progenitor cells (CEPCs) have a pivotal role in the pathophysiology of coronary artery disease (CAD).

Recent data showed an association between history of Hodgkin’s Lymphoma (HL) and increased long-term risk of cardiovascular morbidity and mortality.

Thus, we sought to characterize the CEPCs` profile in HL survivors who were otherwise in a relatively low probability for CAD.

Methods: We isolated CEPCs from peripheral blood samples drawn from 4 groups of patients aged 20-50 years with no history of CAD or diabetes mellitus; 17 HL patients in complete remission (CR) for at least two years; 4 newly diagnosed pre-treated HL patients; 16 healthy individuals (age- sex-matched to the CR group), and 28 diabetic patients.

CEPCs were assessed for expression of VEGFR2, CD133, and CD34, using flow cytometry; the number of colony-forming units (CFUs) and viability using MTT assay.

Results: The pre-treated HL patients had significantly higher levels of CEPCs compared to HL patients in remission (p = 0.03 for CD34(+)/VEGFR2(+) and p = 0.005 for CD133(+)/VEGFR2(+) cells). However, these groups had similarly reduced CEPCs function as expressed in MTT, and the number of CFUs.

The CR HL patients had significantly higher levels of CEPCs compared to diabetic patients (p = 0.011 for CD34(+)/VEGFR2(+) and p < 0.001 for CD133(+)/VEGFR2(+)). However, MTT and CFUs did not differ between these groups.

The CR HL patients had significantly higher levels of CD34(+)/VEGFR2(+) cells (p=0.08) and CD133(+)/VEGFR2(+) cells (p = 0.003) compared to the healthy individuals, albeit reduced CEPCs function reflected by lower MTT (p = 0.005) and CFUs (p <0.001).

Conclusions: CR HL patients, without a typical high-risk profile for CAD, had abnormal CEPCs characterized by increased number though with reduced function as in diabetes mellitus.