Dataset Information

Shotgun LC-MS analysis of aorta and liver tissues from WT and Gal-1 KO mice to study the role of Galectin-1 in vascular remodeling in atherosclerosis and abdominal aortic aneurysm

ABSTRACT: Pathological vascular remodeling is the underlying cause of main cardiovascular diseases (CVD) including atherosclerosis and abdominal aortic aneurysm (AAA). We analyzed the potential role of galectin-1 (Gal-1) in atherosclerosis and AAA. Atherosclerosis was induced in mice lacking Gal-1 (Lgals1-/-) and wild-type (WT) by pAAV/D377Y-mPCSK9 adenovirus injection (1011 vector genome copies) followed by western diet during 16 weeks. In a second model, atherosclerostic WT mice were treated with recombinant Gal-1 protein (rGal-1, 100 µg 3 days/week) or vehicle during 16 weeks. Moreover, the same therapeutic approach was performed in elastase-induced AAA in mice treated for 2 weeks. Finally, Gal-1 expression was assessed in human atherosclerotic plaques and AAA lesions. Gal-1 deletion led to higher atherosclerotic burden along the aorta and larger atherosclerotic plaques in the aortic root. This deleterious effect was associated to higher circulating and lesional lipid levels and lower alpha- smooth muscle actin (α-SMA) staining in the plaques. Proteomic analysis of aorta homogenates showed an upregulation of Fibronectin and VCAM-1 in Lgals1-/- mice as compared to WT aortic tissues. In vitro experiments in VSMCs from Lgals1-/- mice or transfected with Gal-1 siRNA showed increased Fibronectin, VCAM-1 and KLF4 mRNA expression along with a decrease in α-SMA mRNA expression. Treatment with rGal-1 decreased atherosclerotic plaques (size and burden) and elastase-induced aortic dilatation, associated to higher content of α-SMA staining, in both experimental models. Gal-1 protein and mRNA tissue levels were decreased in human atherosclerotic plaques and AAA as compared to control aortic tissues.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver, Abdominal Aorta

DISEASE(S): Atherosclerosis,Abdominal Aortic Aneurysm

SUBMITTER: Estefanía Núñez

LAB HEAD: Jesús Vázquez

PROVIDER: PXD024637 | Pride | 2022-04-04

REPOSITORIES: Pride

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Publications

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

Roldán-Montero Raquel R Pérez-Sáez Juan M JM Cerro-Pardo Isabel I Oller Jorge J Martinez-Lopez Diego D Nuñez Estefania E Maller Sebastian M SM Gutierrez-Muñoz Carmen C Mendez-Barbero Nerea N Escola-Gil Joan C JC Michel Jean-Baptiste JB Mittelbrunn Maria M Vázquez Jesús J Blanco-Colio Luis M LM Rabinovich Gabriel A GA Martin-Ventura Jose L JL

Science advances 20220316 11

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 (<i>Lgals1<sup>-/-</sup></i>) 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 ...[more]

PMID: 35294231

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Project description:Regression of atherosclerosis is an important clinical goal, however the pathways that mediate the resolution of atherosclerotic inflammation and reversal of plaques are poorly understood. Regulatory T cells (Tregs) have been shown to be atheroprotective, however numbers of these immunosuppressive cells decrease with disease progression. Using multiple independent mouse models of atherosclerosis regression, we demonstrate that an increase in plaque Tregs is a common signature of regressing plaques. To test if Tregs are required for the resolution of atherosclerotic inflammation and plaque regression during lipid-lowering therapy, we combined CD25 monoclonal antibody (PC61 mAb)-mediated Treg depletion with single-cell RNA-sequencing of immune cells in the plaque and conventional analyses of atherosclerosis. Single cell RNA-sequencing revealed that Tregs from aortic plaques shared some similarity with splenic Tregs, but were distinct from skin and colon Tregs supporting recent findings of tissue-dependent Treg heterogeneity. Furthermore, Tregs from progressing plaques expressed markers of natural Tregs derived from the thymus, whereas Tregs in regressing plaques lacked Nrp1 and Helios expression, suggesting that they are induced in the periphery during lipid lowering. Treatment of atherosclerotic mice with PC61 mAb effectively depleted Tregs in the blood and peripheral tissues, including plaques, and blocked the regression of atherosclerosis induced by apoB anti-sense oligonucleotides. Morphometric analyses revealed that control antibody-treated mice showed a 40% decrease in plaque burden and macrophage content under regression conditions, whereas PC61 mAb-treated mice showed no change in plaque size or inflammatory cell content compared to baseline. Moreover, Treg depletion enhanced inflammatory signaling and blocked tissue reparative functions of macrophages in the regressing plaque, including M2-polarization, efferocytosis and sensing of specialized pro-resolving lipid mediators. Together, these data establish essential roles for Tregs in the resolution of atherosclerotic inflammation and plaque remodeling during regression.

Dataset Information

Shotgun LC-MS analysis of aorta and liver tissues from WT and Gal-1 KO mice to study the role of Galectin-1 in vascular remodeling in atherosclerosis and abdominal aortic aneurysm

Publications

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

Similar Datasets

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