PB1255 - Disclosing the role of endothelial dysfunction in the pathogenesis of unprovoked venous thromboembolism by using patient-specific endothelial colony-forming cells

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

AC

Assunta Cancellara

PhD student
Unit of Clinical and Experimental Immunology (UCEI), Department of Medical Biotechnologies and Translational Medicine, University of Milan; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
Rozzano, Lombardia, Italy

Co-Author(s)

MB

Monica Bacci

Biologist specialized in clinical biochemistry
Center for Thrombosis and Hemorrhagic Diseases, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
Rozzano, Lombardia, Italy
LB

Lavinia Bertolani

Lab manager and technician
Unit of Clinical and Experimental Immunology (UCEI); IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
Rozzano, Lombardia, Italy
ER

Erica Romualdi

MD; PhD; Staff physician
UO Medicina 2, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, Varese, Italy
Varese, Lombardia, Italy
VP

Valentina Pessi

MD, Resident
Università dell'Insubria - Dipartimento di Medicina e Chirurgia, Varese, Italy
Varese, Lombardia, Italy
CL

Corrado Lodigiani

MD; PhD; Center Responsible
Center for Thrombosis and Hemorrhagic Diseases, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
Rozzano, Lombardia, Italy
MD

Marco Paolo Donadini

MD, Associate Professor
Centro Trombosi ed Emostasi, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, Varese, Italy
Varese, Lombardia, Italy
SD

Silvia Della Bella

MD, PhD, Associate Professor
Unit of Clinical and Experimental Immunology (UCEI) - Department of Medical Biotechnologies and Translational Medicine, University of Milan, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
Rozzano, Lombardia, Italy
FC

Francesca Calcaterra

PhD, Staff Scientist
Unit of Clinical and Experimental Immunology (UCEI) - Department of Medical Biotechnologies and Translational Medicine, University of Milan; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
Rozzano, Lombardia, Italy
DM

Domenico Mavilio

MD, PhD, Full Professor – Head of UCEI
Unit of Clinical and Experimental Immunology (UCEI) - Department of Medical Biotechnologies and Translational Medicine, University of Milan, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
Rozzano, Lombardia, Italy

Background: Venous thromboembolism (VTE) is a multifactorial disease that often occurs in the presence of provoking factors; major risk factors induced provoked VTE (pVTE) whereas weakly provoked (wpVTE) is associated with minor ones. Nevertheless, up to 50% of VTE events are defined as unprovoked (uVTE) as their pathogenesis is still unknown. In this regard, the presence of endothelial alterations deserves to be explored as endothelial dysfunction (ED) is known to trigger thrombus formation. Endothelial colony-forming cells (ECFCs) are the true endothelial progenitors proposed as cell therapy product or liquid biopsy in vascular disorders.

Aims: To investigate whether ECFCs in VTE patients show alterations that may reflect a perturbation of the endothelial compartment involved in uVTE pathogenesis.

Methods: ECFCs were isolated and expanded from peripheral blood mononuclear cells obtained from 40 VTE patients (13 uVTE, 16 wpVTE, 11 pVTE) and 10 matched healthy donors (HDs). ECFCs were analyzed for efficiency of isolation, cell viability and growth. ED was assessed by in vitro functional assays.

Results: ECFCs were isolated from the three subgroups of VTE patients with a similar efficiency as HDs in term of frequency and number of colonies. In pVTE, a trend in the reduction of the frequency of subjects who gave origin to ECFCs was observed. Time of appearance was longer in VTE with the difference being significant only in wpVTE patients. VTE ECFCs showed a high rate of early senescence (passage≤2), with wpVTE group being characterized by the highest frequency.

Conclusion(s): Our results indicate alterations in the growth of VTE ECFCs thus confirming their use to investigate ED role in uVTE pathogenesis. A deeper characterization of ECFCs, still ongoing, will allow the identification of the molecular mechanisms involved in ED in uVTE and to disclose whether they are associated with uVTE only are shared with secondary VTE.