Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells
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, refer...
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MDPI AG
2020-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/5/1201 |
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| author | Guillaume Bidault Marie Garcia Jacqueline Capeau Romain Morichon Corinne Vigouroux Véronique Béréziat |
| author_facet | Guillaume Bidault Marie Garcia Jacqueline Capeau Romain Morichon Corinne Vigouroux Véronique Béréziat |
| author_sort | Guillaume Bidault |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T19:54:06Z |
| format | Article |
| id | doaj.art-f9c264050c6e4eda976298b9142646af |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:54:06Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f9c264050c6e4eda976298b9142646af2023-11-20T00:11:33ZengMDPI AGCells2073-44092020-05-0195120110.3390/cells9051201Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial CellsGuillaume Bidault0Marie Garcia1Jacqueline Capeau2Romain Morichon3Corinne Vigouroux4Véronique Béréziat5Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), RHU CARMMA, Centre de Recherche Saint-Antoine, INSERM UMR_S 938, Sorbonne Université, 75012 Paris, FranceInstitut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), RHU CARMMA, Centre de Recherche Saint-Antoine, INSERM UMR_S 938, Sorbonne Université, 75012 Paris, FranceInstitut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), RHU CARMMA, Centre de Recherche Saint-Antoine, INSERM UMR_S 938, Sorbonne Université, 75012 Paris, FranceCytometry and Imagery platform Saint-Antoine (CISA), Inserm UMS30 Lumic, 75012 Paris, FranceInstitut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), RHU CARMMA, Centre de Recherche Saint-Antoine, INSERM UMR_S 938, Sorbonne Université, 75012 Paris, FranceInstitut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), RHU CARMMA, Centre de Recherche Saint-Antoine, INSERM UMR_S 938, Sorbonne Université, 75012 Paris, FranceHutchinson–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.https://www.mdpi.com/2073-4409/9/5/1201Hutchinson–Gilford progeria syndrome<i>LMNA</i>progerinlamin Aatherosclerosisendothelial dysfunction |
| spellingShingle | Guillaume Bidault Marie Garcia Jacqueline Capeau Romain Morichon Corinne Vigouroux Véronique Béréziat Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells Cells Hutchinson–Gilford progeria syndrome <i>LMNA</i> progerin lamin A atherosclerosis endothelial dysfunction |
| title | Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells |
| title_full | Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells |
| title_fullStr | Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells |
| title_full_unstemmed | Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells |
| title_short | Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells |
| title_sort | progerin expression induces inflammation oxidative stress and senescence in human coronary endothelial cells |
| topic | Hutchinson–Gilford progeria syndrome <i>LMNA</i> progerin lamin A atherosclerosis endothelial dysfunction |
| url | https://www.mdpi.com/2073-4409/9/5/1201 |
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