Defective Mitochondrial Respiration in Hereditary Thoracic Aneurysms.
Thoracic aortic aneurysms are life-threatening vascular conditions linked to inherited disorders such as Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, and familial thoracic aortic aneurysms and dissections. While traditionally associated with the extracellular matrix and co...
| Autores: | , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Recursos: | Universidad Alfonso X el Sabio |
| Repositorio: | Repositorio Institucional de la Universidad Alfonso X el Sabio |
| Idioma: | inglés |
| OAI Identifier: | oai:archive.uax.com:20.500.12080/54785 |
| Acesso em linha: | https://hdl.handle.net/20.500.12080/54785 |
| Access Level: | acceso abierto |
| Palavra-chave: | Síndrome de Loeys-Dietz Síndrome de Marfan Aneurisma Aneurisma aórtico torácico familiar Mitocondrias Nicotinamida ribósido Células musculares de Smith vasculares |
| Resumo: | Thoracic aortic aneurysms are life-threatening vascular conditions linked to inherited disorders such as Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, and familial thoracic aortic aneurysms and dissections. While traditionally associated with the extracellular matrix and contractile defects in vascular smooth muscle cells, emerging evidence suggests the key role of mitochondrial dysfunction. Here, we show that the overexpression of ACTA2R179H and TGFBR2G357W in murine aortic VSMCs reduces Mitochondrial Transcription Factor A (Tfam) expression, decreases mitochondrial DNA (mtDNA) content, and impairs oxidative phosphorylation, shifting metabolism toward glycolysis. Notably, nicotinamide riboside, a NAD+ precursor, restores mitochondrial respiration, increases Tfam and mtDNA levels, and promotes a contractile phenotype by enhancing actin polymerization and reducing matrix metalloproteinase activity. These findings identify mitochondrial dysfunction as a shared feature in hereditary thoracic aortic aneurysm, not only in Marfan syndrome, but also in other genetic forms, and highlight mitochondrial boosters as a potential therapeutic strategy. |
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