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Cells
Volume 9
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10.3390/cells9051201
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Article

Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells

by
Guillaume Bidault
1,
Marie Garcia
1,
Jacqueline Capeau
1,
Romain Morichon
2,
Corinne Vigouroux
1,3,4 and
Véronique Béréziat
1,*
1
Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), RHU CARMMA, Centre de Recherche Saint-Antoine, INSERM UMR_S 938, Sorbonne Université, 75012 Paris, France
2
Cytometry and Imagery platform Saint-Antoine (CISA), Inserm UMS30 Lumic, 75012 Paris, France
3
Laboratoire Commun de Biologie et Génétique Moléculaires, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France
4
Service d’Endocrinologie, Diabétologie et Endocrinologie de la Reproduction, Centre National de Référence des Pathologies Rares de l’Insulino-Sécrétion et de l’Insulino-Sensibilité (PRISIS), Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France
*
Author to whom correspondence should be addressed.
Cells 2020, 9(5), 1201; https://doi.org/10.3390/cells9051201
Received: 11 April 2020 / Revised: 6 May 2020 / Accepted: 9 May 2020 / Published: 12 May 2020
(This article belongs to the Collection Lamins and Laminopathies)
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Abstract

Hutchinson–Gilford progeria syndrome (HGPS) is a rare premature aging disorder notably characterized by precocious and deadly atherosclerosis. Almost 90% of HGPS patients carry a LMNA p.G608G splice variant that leads to the expression of a permanently farnesylated abnormal form of prelamin-A, referred to as progerin. Endothelial dysfunction is a key determinant of atherosclerosis, notably during aging. Previous studies have shown that progerin accumulates in HGPS patients’ endothelial cells but also during vascular physiological aging. However, whether progerin expression in human endothelial cells can recapitulate features of endothelial dysfunction is currently unknown. Herein, we evaluated the direct impact of exogenously expressed progerin and wild-type lamin-A on human endothelial cell function and senescence. Our data demonstrate that progerin, but not wild-type lamin-A, overexpression induces endothelial cell dysfunction, characterized by increased inflammation and oxidative stress together with persistent DNA damage, increased cell cycle arrest protein expression and cellular senescence. Inhibition of progerin prenylation using a pravastatin–zoledronate combination partly prevents these defects. Our data suggest a direct proatherogenic role of progerin in human endothelial cells, which could contribute to HGPS-associated early atherosclerosis and also potentially be involved in physiological endothelial aging participating to age-related cardiometabolic diseases. View Full-Text
Keywords: Hutchinson–Gilford progeria syndrome; LMNA; progerin; lamin A; atherosclerosis; endothelial dysfunction; inflammation; prenylation; aging Hutchinson–Gilford progeria syndrome; LMNA; progerin; lamin A; atherosclerosis; endothelial dysfunction; inflammation; prenylation; aging
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Bidault, G.; Garcia, M.; Capeau, J.; Morichon, R.; Vigouroux, C.; Béréziat, V. Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells. Cells 2020, 9, 1201. https://doi.org/10.3390/cells9051201

AMA Style

Bidault G, Garcia M, Capeau J, Morichon R, Vigouroux C, Béréziat V. Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells. Cells. 2020; 9(5):1201. https://doi.org/10.3390/cells9051201

Chicago/Turabian Style

Bidault, Guillaume, Marie Garcia, Jacqueline Capeau, Romain Morichon, Corinne Vigouroux, and Véronique Béréziat. 2020. "Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells" Cells 9, no. 5: 1201. https://doi.org/10.3390/cells9051201

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