Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease-Reference-Cited by-同舟云学术

Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease

Published:2020-11-05 Issue: Volume: Page:
ISSN:1079-5642
Container-title:Arteriosclerosis, Thrombosis, and Vascular Biology
language:en
Short-container-title:ATVB

Author:

Gendron Nicolas¹²,Rosa Mickael³,Blandinieres Adeline¹²,Sottejeau Yoann³,Rossi Elisa¹²,Van Belle Eric³^ORCID,Idelcadi Salim¹⁴,Lecourt Séverine¹²,Vincentelli André³,Cras Audrey¹⁵^ORCID,Jashari Ramadan⁶,Chocron Richard⁷⁸^ORCID,Baudouin Yaël⁹,Pamart Thibault³,Bièche Ivan¹⁰,Nevo Nathalie¹²^ORCID,Cholley Bernard⁴^ORCID,Rancic Jeanne¹²,Staels Bart³^ORCID,Gaussem Pascale¹²^ORCID,Dupont Annabelle³,Carpentier Alain¹¹,Susen Sophie³^ORCID,Smadja David M.¹²^ORCID

Affiliation:

1. Université de Paris, Innovative Therapies in Haemostasis, INSERM, France (N.G., A.B., E.R., S.I., S.L., A. Cras, N.N., J.R., P.G., D.M.S.).

2. Hematology Department and Biosurgical Research Lab (Carpentier Foundation), AH-HP, Georges Pompidou European Hospital, France. (N.G., A.B., E.R., S.L., N.N., J.R., P.G., D.M.S.)

3. University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, France (M.R., Y.S., E.V.B., A.V., T.P., B.S., A.D., S.S.).

4. Department of Anesthesia and Intensive Care and Biosurgical Research Lab (Carpentier Foundation), AH-HP, Georges Pompidou European Hospital, France. (S.I., B.C.)

5. Cell therapy Department, AH-HP, Saint Louis Hospital, Paris, France (A. Cras).

6. European Homograft Bank, Clinic Saint Jean, Brussels, Belgium (R.J.).

7. Emergency Medicine Department, AH-HP, Georges Pompidou European Hospital, France. (R.C.)

8. Université de Paris, PARCC, INSERM, France (R.C.).

9. Hematology Department, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France (Y.B.).

10. Department of Genetics, Pharmacogenomics Unit, Institut Curie, Paris, France (I.B.).

11. Université de Paris, Biosurgical Research Lab (Carpentier Foundation), AH-HP, Georges Pompidou European Hospital, France. (A. Carpentier)

Abstract

Objective: The study’s aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VIC p ) mesenchymal-like phenotype was confirmed by CD90 + /CD73 + /CD44 + expression and multipotent-like differentiation ability. When VIC p were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VIC p and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VIC p -conditioned media and confirmed at the mRNA level in VIC p compared with control VIC. Conditioned media from VIC p induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VIC p involvement in angiogenesis by a VEGF-A dependent mechanism. Conclusions: We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VIC p in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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