Galectin-1 prevents pathological vascular remodeling in atherosclerosis and abdominal aortic aneurysm
Raquel Roldán-Montero, Juan M. Pérez‐Sáez, Isabel Cerro-Pardo, Jorge Oller, Diego Martínez-López, Estefanía Núñez, Sebastián M. Maller, Carmen Gutiérrez‐Muñoz, Nerea Méndez‐Barbero, Joan Carles Escolá‐Gil, Jean-Baptiste Michel, Marı́a Mittelbrunn, Jesús Vázquez, Luis Miguel Blanco‐Colio, Gabriel A. Rabinovich, José Luis Martı́n-Ventura
Abstract
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.