Galectin-1 prevents pathological vascular remodeling in atherosclerosis and abdominal aortic aneurysm.

Pathological vascular remodeling is the underlying cause of atherosclerosis and abdominal aortic aneurysm (AAA). Here, we analyzed the role of galectin-1 (Gal-1), a β-galactoside-binding protein, as a therapeutic target for atherosclerosis and AAA. Mice lacking Gal-1 (Lgals1-/-) developed severe ath...

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Detalles Bibliográficos
Autores: Roldán-Montero, Raquel, Pérez-Sáez, Juan M, Cerro-Pardo, Isabel, Oller, Jorge, Martinez-Lopez, Diego, Nunez, Estefania, Maller, Sebastian M, Gutierrez-Muñoz, Carmen, Mendez-Barbero, Nerea, Escola-Gil, Joan C, Michel, Jean-Baptiste, Mittelbrunn, Maria, Vazquez, Jesus, Blanco-Colio, Luis M, Rabinovich, Gabriel A, Martin-Ventura, Jose L
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/15264
Acceso en línea:http://hdl.handle.net/20.500.12105/15264
Access Level:acceso abierto
Palabra clave:Aortic Aneurysm, Abdominal
Atherosclerosis
Animals
Disease Models, Animal
Galectin 1
Mice
Mice, Inbred C57BL
Muscle, Smooth, Vascular
Proteomics
Vascular Remodeling
Descripción
Sumario:Pathological vascular remodeling is the underlying cause of atherosclerosis and abdominal aortic aneurysm (AAA). Here, we analyzed the role of galectin-1 (Gal-1), a β-galactoside-binding protein, as a therapeutic target for atherosclerosis and AAA. Mice lacking Gal-1 (Lgals1-/-) developed severe atherosclerosis induced by pAAV/D377Y-mPCSK9 adenovirus and displayed higher lipid levels and lower expression of contractile markers of vascular smooth muscle cells (VSMCs) in plaques than wild-type mice. Proteomic analysis of Lgals1-/- aortas showed changes in markers of VSMC phenotypic switch and altered composition of mitochondrial proteins. Mechanistically, Gal-1 silencing resulted in increased foam cell formation and mitochondrial dysfunction in VSMCs, while treatment with recombinant Gal-1 (rGal-1) prevented these effects. Furthermore, rGal-1 treatment attenuated atherosclerosis and elastase-induced AAA, leading to higher contractile VSMCs in aortic tissues. Gal-1 expression decreased in human atheroma and AAA compared to control tissue. Thus, Gal-1-driven circuits emerge as potential therapeutic strategies in atherosclerosis and AAA.

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