Altered endothelial mitochondrial Opa1‐related fusion in mouse accelerates age‐associated vascular and kidney damage
Abstract Cardiovascular diseases are the major cause of death worldwide, and their frequency increases with age in association with kidney damage. As a reduction in fusion protein optic atrophy type 1 (Opa1) level in endothelial cells (ECs) decreases the vascular response to flow and increases oxida...
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| Format: | Article |
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Wiley
2025-07-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.70451 |
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| author | Carlotta Turnaturi Loïck L'Hoste Coralyne Proux Linda Grimaud Emilie Vessieres Antonio Zorzano Anne Teissier Pascal Reynier Raffaella Sorrentino Guy Lenaers Laurent Loufrani Daniel Henrion |
| author_facet | Carlotta Turnaturi Loïck L'Hoste Coralyne Proux Linda Grimaud Emilie Vessieres Antonio Zorzano Anne Teissier Pascal Reynier Raffaella Sorrentino Guy Lenaers Laurent Loufrani Daniel Henrion |
| author_sort | Carlotta Turnaturi |
| collection | DOAJ |
| description | Abstract Cardiovascular diseases are the major cause of death worldwide, and their frequency increases with age in association with kidney damage. As a reduction in fusion protein optic atrophy type 1 (Opa1) level in endothelial cells (ECs) decreases the vascular response to flow and increases oxidative stress in perfused kidneys, we hypothesized that reduced Opa1 expression contributes to vascular aging. We used male and female mice with ECs specific Opa1 knock‐out (EC‐Opa1), and littermate wild‐type (EC‐WT) mice aged 6 (young) and 20 months (old). Mesenteric resistance arteries (MRA) and kidneys were collected for vascular reactivity and western‐blot analysis. In old EC‐Opa1 mice, blood urea was greater than in EC‐WT mice, and MRA showed reduced endothelium‐dependent relaxation. In kidneys, the mitochondria fission protein fission‐1 (Fis‐1) and the peroxisome proliferator‐activated receptor gamma coactivator‐1 alpha (Pgc‐1α) were increased in old EC‐Opa1 mice. The level of caveolin‐1 expression was greater in old EC‐Opa1 mice. Moreover, in kidneys from EC‐Opa1 old mice, NADPH‐oxidase subunit gp91 expression was greater than in age‐matched EC‐WT mice. Thus, reduced mitochondrial fusion in mouse ECs altered mesenteric vascular reactivity and increased markers of oxidative stress in aging kidneys. Thus, Opa1 might protect the vascular tree in target organs such as the kidney. |
| format | Article |
| id | doaj-art-69ee346d651b40f696e7229aa0f669dd |
| institution | Kabale University |
| issn | 2051-817X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-69ee346d651b40f696e7229aa0f669dd2025-08-20T03:50:49ZengWileyPhysiological Reports2051-817X2025-07-011313n/an/a10.14814/phy2.70451Altered endothelial mitochondrial Opa1‐related fusion in mouse accelerates age‐associated vascular and kidney damageCarlotta Turnaturi0Loïck L'Hoste1Coralyne Proux2Linda Grimaud3Emilie Vessieres4Antonio Zorzano5Anne Teissier6Pascal Reynier7Raffaella Sorrentino8Guy Lenaers9Laurent Loufrani10Daniel Henrion11Univ Angers, INSERM, CNRS, MITOVASC Dept, CARME Team, SFR ICAT Angers FranceUniv Angers, INSERM, CNRS, MITOVASC Dept, CARME Team, SFR ICAT Angers FranceUniv Angers, INSERM, CNRS, MITOVASC Dept, CARME Team, SFR ICAT Angers FranceUniv Angers, INSERM, CNRS, MITOVASC Dept, CARME Team, SFR ICAT Angers FranceUniv Angers, INSERM, CNRS, MITOVASC Dept, CARME Team, SFR ICAT Angers FranceInstitute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology Barcelona SpainDepartment of Biochemistry and Molecular Biology University Hospital of Angers Angers FranceUniv Angers, INSERM, CNRS, MITOVASC Dept, CARME Team, SFR ICAT Angers FranceDepartment of Pharmacy, School of Medicine and Surgery University of Naples Federico II Naples ItalyDepartment of Pharmacy, School of Medicine and Surgery University of Naples Federico II Naples ItalyUniv Angers, INSERM, CNRS, MITOVASC Dept, CARME Team, SFR ICAT Angers FranceUniv Angers, INSERM, CNRS, MITOVASC Dept, CARME Team, SFR ICAT Angers FranceAbstract Cardiovascular diseases are the major cause of death worldwide, and their frequency increases with age in association with kidney damage. As a reduction in fusion protein optic atrophy type 1 (Opa1) level in endothelial cells (ECs) decreases the vascular response to flow and increases oxidative stress in perfused kidneys, we hypothesized that reduced Opa1 expression contributes to vascular aging. We used male and female mice with ECs specific Opa1 knock‐out (EC‐Opa1), and littermate wild‐type (EC‐WT) mice aged 6 (young) and 20 months (old). Mesenteric resistance arteries (MRA) and kidneys were collected for vascular reactivity and western‐blot analysis. In old EC‐Opa1 mice, blood urea was greater than in EC‐WT mice, and MRA showed reduced endothelium‐dependent relaxation. In kidneys, the mitochondria fission protein fission‐1 (Fis‐1) and the peroxisome proliferator‐activated receptor gamma coactivator‐1 alpha (Pgc‐1α) were increased in old EC‐Opa1 mice. The level of caveolin‐1 expression was greater in old EC‐Opa1 mice. Moreover, in kidneys from EC‐Opa1 old mice, NADPH‐oxidase subunit gp91 expression was greater than in age‐matched EC‐WT mice. Thus, reduced mitochondrial fusion in mouse ECs altered mesenteric vascular reactivity and increased markers of oxidative stress in aging kidneys. Thus, Opa1 might protect the vascular tree in target organs such as the kidney.https://doi.org/10.14814/phy2.70451agingarteriesendothelial cellkidneymitochondrial fusion |
| spellingShingle | Carlotta Turnaturi Loïck L'Hoste Coralyne Proux Linda Grimaud Emilie Vessieres Antonio Zorzano Anne Teissier Pascal Reynier Raffaella Sorrentino Guy Lenaers Laurent Loufrani Daniel Henrion Altered endothelial mitochondrial Opa1‐related fusion in mouse accelerates age‐associated vascular and kidney damage Physiological Reports aging arteries endothelial cell kidney mitochondrial fusion |
| title | Altered endothelial mitochondrial Opa1‐related fusion in mouse accelerates age‐associated vascular and kidney damage |
| title_full | Altered endothelial mitochondrial Opa1‐related fusion in mouse accelerates age‐associated vascular and kidney damage |
| title_fullStr | Altered endothelial mitochondrial Opa1‐related fusion in mouse accelerates age‐associated vascular and kidney damage |
| title_full_unstemmed | Altered endothelial mitochondrial Opa1‐related fusion in mouse accelerates age‐associated vascular and kidney damage |
| title_short | Altered endothelial mitochondrial Opa1‐related fusion in mouse accelerates age‐associated vascular and kidney damage |
| title_sort | altered endothelial mitochondrial opa1 related fusion in mouse accelerates age associated vascular and kidney damage |
| topic | aging arteries endothelial cell kidney mitochondrial fusion |
| url | https://doi.org/10.14814/phy2.70451 |
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