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Article

Interferons Are Pro-Inflammatory Cytokines in Sheared-Stressed Human Aortic Valve Endothelial Cells

by
Iván Parra-Izquierdo
1,†,
Tania Sánchez-Bayuela
1,
Javier López
2,3,
Cristina Gómez
1,
Enrique Pérez-Riesgo
1,
J. Alberto San Román
2,3,
Mariano Sánchez Crespo
1,
Magdi Yacoub
4,5,
Adrian H. Chester
4,5,* and
Carmen García-Rodríguez
1,3,*
1
Instituto de Biología y Genética Molecular, Spanish National Research Council (CSIC), Universidad de Valladolid, 47003 Valladolid, Spain
2
ICICOR, Hospital Clínico Universitario, 47005 Valladolid, Spain
3
Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain
4
National Heart & Lung Institute, Imperial College London, London SW3 6LR, UK
5
Magdi Yacoub Institute, Harefield UB9 6JH, UK
*
Authors to whom correspondence should be addressed.
†
Current address: Knight Cardiovascular Institute and Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
Int. J. Mol. Sci. 2021, 22(19), 10605; https://doi.org/10.3390/ijms221910605
Submission received: 2 August 2021 / Revised: 24 September 2021 / Accepted: 25 September 2021 / Published: 30 September 2021
(This article belongs to the Special Issue Molecular Mechanisms of Aortic Valve Disease)
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Abstract

Calcific aortic valve disease (CAVD) is an athero-inflammatory process. Growing evidence supports the inflammation-driven calcification model, mediated by cytokines such as interferons (IFNs) and tumor necrosis factor (TNF)-α. Our goal was investigating IFNs’ effects in human aortic valve endothelial cells (VEC) and the potential differences between aortic (aVEC) and ventricular (vVEC) side cells. The endothelial phenotype was analyzed by Western blot, qPCR, ELISA, monocyte adhesion, and migration assays. In mixed VEC populations, IFNs promoted the activation of signal transducers and activators of transcription-1 and nuclear factor-κB, and the subsequent up-regulation of pro-inflammatory molecules. Side-specific VEC were activated with IFN-γ and TNF-α in an orbital shaker flow system. TNF-α, but not IFN-γ, induced hypoxia-inducible factor (HIF)-1α stabilization or endothelial nitric oxide synthase downregulation. Additionally, IFN-γ inhibited TNF-α–induced migration of aVEC. Also, IFN-γ triggered cytokine secretion and adhesion molecule expression in aVEC and vVEC. Finally, aVEC were more prone to cytokine-mediated monocyte adhesion under multiaxial flow conditions as compared with uniaxial flow. In conclusion, IFNs promote inflammation and reduce TNF-α–mediated migration in human VEC. Moreover, monocyte adhesion was higher in inflamed aVEC sheared under multiaxial flow, which may be relevant to understanding the initial stages of CAVD.
Keywords: valvular endothelial cells; interferons; monocyte adhesion; inflammation; JAK/STAT valvular endothelial cells; interferons; monocyte adhesion; inflammation; JAK/STAT

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MDPI and ACS Style

Parra-Izquierdo, I.; Sánchez-Bayuela, T.; López, J.; Gómez, C.; Pérez-Riesgo, E.; San Román, J.A.; Sánchez Crespo, M.; Yacoub, M.; Chester, A.H.; García-Rodríguez, C. Interferons Are Pro-Inflammatory Cytokines in Sheared-Stressed Human Aortic Valve Endothelial Cells. Int. J. Mol. Sci. 2021, 22, 10605. https://doi.org/10.3390/ijms221910605

AMA Style

Parra-Izquierdo I, Sánchez-Bayuela T, López J, Gómez C, Pérez-Riesgo E, San Román JA, Sánchez Crespo M, Yacoub M, Chester AH, García-Rodríguez C. Interferons Are Pro-Inflammatory Cytokines in Sheared-Stressed Human Aortic Valve Endothelial Cells. International Journal of Molecular Sciences. 2021; 22(19):10605. https://doi.org/10.3390/ijms221910605

Chicago/Turabian Style

Parra-Izquierdo, Iván, Tania Sánchez-Bayuela, Javier López, Cristina Gómez, Enrique Pérez-Riesgo, J. Alberto San Román, Mariano Sánchez Crespo, Magdi Yacoub, Adrian H. Chester, and Carmen García-Rodríguez. 2021. "Interferons Are Pro-Inflammatory Cytokines in Sheared-Stressed Human Aortic Valve Endothelial Cells" International Journal of Molecular Sciences 22, no. 19: 10605. https://doi.org/10.3390/ijms221910605

APA Style

Parra-Izquierdo, I., Sánchez-Bayuela, T., López, J., Gómez, C., Pérez-Riesgo, E., San Román, J. A., Sánchez Crespo, M., Yacoub, M., Chester, A. H., & García-Rodríguez, C. (2021). Interferons Are Pro-Inflammatory Cytokines in Sheared-Stressed Human Aortic Valve Endothelial Cells. International Journal of Molecular Sciences, 22(19), 10605. https://doi.org/10.3390/ijms221910605

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