Galectin-3 interferes with tissue repair and promotes cardiac dysfunction and comorbidities in a genetic heart failure model

Vlachou, Fani; Varela, Aimilia; Σταθοπούλου, Κωνσταντίνα; Ntatsoulis, Konstantinos; Synolaki, Evgenia; Pratsinis, Harris; Kletsas, Dimitris; Sideras, Paschalis; Davos, Constantinos H.; Capetanaki, Yassemi; Psarras, Stelios

doi:10.1007/s00018-022-04266-6

Cited by 21 publications

(8 citation statements)

References 61 publications

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“…Gal-3 was found to be causally involved in cardiac adverse remodeling, inflammation, and failure by affecting the functions of cardiac fibroblasts and macrophages. It promoted pro-fibrotic responses while at the same time inhibiting the repair of the damaged myocardium ( 38 ). However, Lgals3 −/− mice demonstrated less home cage movement and more perturbation of behavioral circadian rhythms as compared to wild-type controls ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

High blood galectin-3 level associated with risk of frailty in aging

Ji,

Jiang,

Qiu

et al. 2023

Front. Endocrinol.

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BackgroundFrailty is one of the most problematic expressions of population aging, but its underlying mechanism has not been fully elucidated. Circulating galectin-3 (Gal-3) is involved in the pathogenesis of many age-related diseases. This study aims to explore the influence of circulating Gal-3 on the regulation of frailty and aging and to identify the potential mechanism further.MethodsIn this cross-sectional analysis, the Fried frailty phenotype (FP) was assessed among 149 community elderly residents in Shanghai. Peripheral blood mononuclear cells (PBMCs) were isolated by the Ficoll-Paque density gradient method, and differentially expressed genes (DEGs) encoding transcription factors in frailty were detected by Illumina and bioinformatics analyzed with R software. Gene Ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the functional roles of these DEGs and the target genes related to frailty phenotypes. The serum Gal-3 concentration was tested by enzyme-linked immunosorbent assay (ELISA). Mouse frailty phenotype was used to construct an in vivo model of frailty, after which the serum levels of circulating Gal-3 and its gene expression levels in mouse tissues were determined.ResultsParticipants’ mean age was 72.04 ± 7.05 years. In total, 21.48% were frail and 36.91% were pre-frail. The mean serum Gal-3 concentration was 46.34 ± 17.99 ng/mL in frail participants, 32.30 ± 8.14 ng/mL in pre-frail participants, and 26.00 ± 5.87 ng/mL in non-frail individuals (p < 0.001). Significant positive correlations between serum Gal-3 level and FP score, SARC-F score, C-reactive protein (CRP), interleukin-6, etc., were observed. In addition, the KEGG pathway and GO enrichment analyses showed that 265 DEGs in PBMCs of frail participants were mainly related to inflammatory response, translation, RNA binding, protein binding, ribosome, and primary immunodeficiency. LGALS3 was identified as the overlapping gene between frailty-related DEGs and aging-related DEGs. The elevated serum Gal-3 concentration in the in vivo model of frailty was consistent with the results in participants.ConclusionIn both community-dwelling older adults and aged mice, serum Gal-3 concentration was positively correlated with frailty. This circulating mediator may be a promising indicator of frailty.Clinical trial registrationChinese Clinical Trial Registry identifier, ChiCTR2000036399.

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Section: Discussionmentioning

confidence: 99%

High blood galectin-3 level associated with risk of frailty in aging

Ji,

Jiang,

Qiu

et al. 2023

Front. Endocrinol.

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“…During the development of des -/cardiomyopathy, Galectin-3 deficiency downregulated CCR2, Arg1 and pro-fibrotic gene expression as well as amelioration of poor cardiac remodeling, inflammation and failure (13).…”

Section: Ccl2-ccr2 Axis and Cardiovascular Disease Ccl2-ccr2 Axis And...mentioning

confidence: 98%

“…This model is accompanied by macrophage infiltration and upregulation of the deleterious macrophage-associated genes CCR2 and Arg1. During the development of des -/- cardiomyopathy, Galectin-3 deficiency downregulated CCR2, Arg1 and pro-fibrotic gene expression as well as amelioration of poor cardiac remodeling, inflammation and failure ( 13 ).…”

Section: Ccl2-ccr2 Axis and Cardiovascular Diseasementioning

confidence: 99%

“…Rats with suprarenal aortic constriction CCL2-mediated macrophage aggregation acted on myocardial fibrosis via a TGF-b-mediated process (12) Genetic HF Des -/mice Downregulation of CCR2, Arg1 and pro-fibrotic gene expression ameliorated poor cardiac remodeling, inflammation and failure (13) End-stage HF Hearts from patients with end-stage HF and in organ donors First demonstrated the expression and protein localization of CCL2/ CCR2 in human myocardium (14) CHF CHF patients Serum CCL2 levels were positively related to the seriousness of symptoms as well as the degree of left heart insufficiency in patients with CHF (15) Advanced HF Advanced HF patients CCL2 was significantly associated with poor prognosis in patients with advanced heart failure (16)…”

Section: Hypertensive Heart Diseasementioning

confidence: 99%

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Role of the CCL2-CCR2 axis in cardiovascular disease: Pathogenesis and clinical implications

et al. 2022

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The CCL2-CCR2 axis is one of the major chemokine signaling pathways that has received special attention because of its function in the development and progression of cardiovascular disease. Numerous investigations have been performed over the past decades to explore the function of the CCL2-CCR2 signaling axis in cardiovascular disease. Laboratory data on the CCL2-CCR2 axis for cardiovascular disease have shown satisfactory outcomes, yet its clinical translation remains challenging. In this article, we describe the mechanisms of action of the CCL2-CCR2 axis in the development and evolution of cardiovascular diseases including heart failure, atherosclerosis and coronary atherosclerotic heart disease, hypertension and myocardial disease. Laboratory and clinical data on the use of the CCL2-CCR2 pathway as a targeted therapy for cardiovascular diseases are summarized. The potential of the CCL2-CCR2 axis in the treatment of cardiovascular diseases is explored.

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“…Therefore, Gal-3 inhibition has been considered a potential target in curing MF [ 7 , 8 ]. Preclinical studies have reported that pharmacological and genetic inhibition of Gal-3 confers effects with reduction of MF [ 9 , 10 ]. Modified citrus pectin (MCP) and N-acetyllactosamine, inhibitors of Gal-3, ameliorated MF and inflammation in various rodent and mice models [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Ultrasonic Microbubble Cavitation Deliver Gal-3 shRNA to Inhibit Myocardial Fibrosis after Myocardial Infarction

Jin

Zhang

et al. 2023

Pharmaceutics

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Galectin-3 (Gal-3) participates in myocardial fibrosis (MF) in a variety of ways. Inhibiting the expression of Gal-3 can effectively interfere with MF. This study aimed to explore the value of Gal-3 short hairpin RNA (shRNA) transfection mediated by ultrasound-targeted microbubble destruction (UTMD) in anti-myocardial fibrosis and its mechanism. A rat model of myocardial infarction (MI) was established and randomly divided into control and Gal-3 shRNA/cationic microbubbles + ultrasound (Gal-3 shRNA/CMBs + US) groups. Echocardiography measured the left ventricular ejection fraction (LVEF) weekly, and the heart was harvested to analyze fibrosis, Gal-3, and collagen expression. LVEF in the Gal-3 shRNA/CMB + US group was improved compared with the control group. On day 21, the myocardial Gal-3 expression decreased in the Gal-3 shRNA/CMBs + US group. Furthermore, the proportion of the myocardial fibrosis area in the Gal-3 shRNA/CMBs + US group was 6.9 ± 0.41% lower than in the control group. After inhibition of Gal-3, there was a downregulation in collagen production (collagen I and III), and the ratio of Col I/Col III decreased. In conclusion, UTMD-mediated Gal-3 shRNA transfection can effectively silence the expression of Gal-3 in myocardial tissue, reduce myocardial fibrosis, and protect the cardiac ejection function.

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Galectin-3 interferes with tissue repair and promotes cardiac dysfunction and comorbidities in a genetic heart failure model

Cited by 21 publications

References 61 publications

High blood galectin-3 level associated with risk of frailty in aging

High blood galectin-3 level associated with risk of frailty in aging

Role of the CCL2-CCR2 axis in cardiovascular disease: Pathogenesis and clinical implications

Ultrasonic Microbubble Cavitation Deliver Gal-3 shRNA to Inhibit Myocardial Fibrosis after Myocardial Infarction

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