Functional Impairment of Endothelial Colony Forming Cells (ECFC) in Patients with Severe Atherosclerotic Cardiovascular Disease (ASCVD)

Stéphanie Simoncini (1) , Simon Toupance (2) , Carlos Labat (2) , Sylvie Gautier (3, 4) , Chloé Dumoulin (5) , Laurent Arnaud (6) , Maria Stathopoulou (7) , Sophie Visvikis-Siest (8) , Pascal Rossi (1, 9) , Athanase Benetos (2, 3) , Françoise Dignat-George (1, 6) , Florence Sabatier (1, 5)

1 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
2 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
3 Service de Gériatrie [CHRU Nancy]
4 UL - Université de Lorraine
5 CIC - Centre d'Investigation Clinique [Hôpital de la Conception - APHM]
6 TIMONE - Hôpital de la Timone [CHU - APHM]
7 C3M - Centre méditerranéen de médecine moléculaire
8 IGE-PCV - Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire
9 Hôpital Nord [CHU - APHM]

Endothelial dysfunction is a key factor in atherosclerosis. However, the link between endothelial repair and severity of atherosclerotic cardiovascular disease (ASCVD) is unclear. This study investigates the relationship between ASCVD, markers of inflammation, and circulating endothelial progenitor cells, namely hematopoietic cells with paracrine angiogenic activity and endothelial colony forming cells (ECFC). Two hundred and forty-three subjects from the TELARTA study were classified according to the presence of clinical atherosclerotic disease. ASCVD severity was assessed by the number of involved vascular territories. Flow cytometry was used to numerate circulating progenitor cells (PC) expressing CD34 and those co-expressing CD45, CD34, and KDR. Peripheral blood mononuclear cells ex vivo culture methods were used to determine ECFC and Colony Forming Unit- endothelial cells (CFU-EC). The ECFC subpopulation was analyzed for proliferation, senescence, and vasculogenic properties. Plasma levels of IL-6 and VEGF-A were measured using Cytokine Array. Despite an increased number of circulating precursors in ASCVD patients, ASCVD impaired the colony forming capacity and the angiogenic properties of ECFC in a severity-dependent manner. Alteration of ECFC was associated with increased senescent phenotype and IL-6 levels. Our study demonstrates a decrease in ECFC repair capacity according to ASCVD severity in an inflammatory and senescence-associated secretory phenotype context.

Mots clés: endothelial progenitor cells; atherosclerosis; senescence

Domaines: Sciences du Vivant [q-bio]

Stéphanie Simoncini, Simon Toupance, Carlos Labat, Sylvie Gautier, Chloé Dumoulin, et al.. Functional Impairment of Endothelial Colony Forming Cells (ECFC) in Patients with Severe Atherosclerotic Cardiovascular Disease (ASCVD). International Journal of Molecular Sciences, 2022, 23 (16), pp.8969. ⟨10.3390/ijms23168969⟩. ⟨hal-03792052⟩