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

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.

• Authors: Raquel Roldán-Montero, Juan M Pérez-Sáez, Isabel Cerro-Pardo, Jorge Oller, Diego Martinez-Lopez, Estefania Nuñez, Sebastian M Maller, Carmen Gutierrez-Muñoz, Nerea Mendez-Barbero, Joan C Escola-Gil, Jean-Baptiste Michel, Maria Mittelbrunn, Jesús Vázquez, Luis M Blanco-Colio, Gabriel A Rabinovich, Jose L Martin-Ventura
• Journal: Science advances (Sci Adv) Vol. 8 Issue 11 Pg. eabm7322 (03 18 2022) ISSN: 2375-2548 [Electronic] United States
• PMID: 35294231 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Galectin 1

Topics

• Animals
• Aortic Aneurysm, Abdominal (etiology, metabolism, pathology)
• Atherosclerosis (genetics, metabolism)
• Disease Models, Animal
• Galectin 1 (genetics, metabolism, pharmacology)
• Mice
• Mice, Inbred C57BL
• Muscle, Smooth, Vascular (metabolism, pathology)
• Proteomics
• Vascular Remodeling