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.

Vascular Smooth Muscle Cells Phenotypic Switching in Cardiovascular Diseases

“…Galectin-1 (Gal-1) is a galactoside-binding protein that may serve as a new target for the treatment of atherosclerosis. Mice deficient in Gal-1 (Lgals1 −/− ) develop severe atherosclerosis with increased lipid levels in plaques and reduced expression of contractile markers in VSMCs compared to wild-type mice [ 36 ] ( Table 1 ). The plaque volume is reduced, intraplaque oxidized low-density lipoprotein (ox-LDL) was significantly reduced, and the phenotypic transformation of VSMCs was suppressed in plaque-prone apolipoprotein E and CRP4 double knockout (dKO) mice [ 37 ].…”

Identification of core cuprotosis-correlated biomarkers in abdominal aortic aneurysm immune microenvironment based on bioinformatics

“…In our previous study, macrophage NLRP3 inflammasome plays a significant role in promoting the progress of AAA ( 5 ). Furthermore, NLRP3 inflammasome activation regulates vascular smooth muscle cells phenotypic switch ( 49 ), which ultimately leads to AAA development through tunica medium elastin degradation ( 4 ). However, few studies have demonstrated the role and potential mechanism of FDX1 in AAA formation, which may become a promising research orientation.…”

“…In various studies, lipid peroxidation exerts significant influence on cardiovascular diseases including atherosclerosis and AAA ( 2 , 3 ). Meanwhile, AAA is the late stage of atherosclerosis ( 4 ). Furthermore, inflammation has been demonstrated to play vital role in AAA pathology.…”

Activated leukocyte cell adhesion molecule/cluster of differentiation 166 rs10933819 (G>A) variant is associated with familial intracranial aneurysms

“…T hus, A LCA M physica l ly i nteracts wit h t he T cell-expressed scavenger receptor CD6, endothelial L1CAM, and galectin-8 (24). Notably, the other lectins, namely galectin-1 and galectin-3, have been reported to be associated with abdominal aortic aneurysms (26,27).…”