Macrophages and galectin 3 play critical roles in CVB3-induced murine acute myocarditis and chronic fibrosis

Giusti, C; Ure, Agustín Enrique; Rivadeneyra, Leonardo; Schattner, Mirta; Gómez, Ricardo Martín

doi:10.1016/j.yjmcc.2015.05.010

Cited by 65 publications

(60 citation statements)

References 59 publications

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“…First, when tested ex vivo, Gal-3 promoted fibroblast proliferation and expression of fibrogenic genes (Frunza et al, 2016;Ibarrola et al, 2018;Mackinnon et al, 2012;Takemoto et al, 2016;Vergaro et al, 2016;Yu et al, 2013). Gal-3 also promoted the innate immune response by stimulating monocyte migration and expression of inflammatory cytokines and chemokines (Jaquenod De Giusti et al, 2015;Nachtigal et al, 2008;Sharma et al, 2004;Vasta, 2012). Moreover, in a rat study, chronic delivery of Gal-3 via implanted osmotic minipump with a cannula inserted into the pericardium caused cardiac histopathology including fibrosis (Sharma et al, 2004).…”

Section: In Heart Diseasementioning

confidence: 99%

“…Moreover, in a rat study, chronic delivery of Gal-3 via implanted osmotic minipump with a cannula inserted into the pericardium caused cardiac histopathology including fibrosis (Sharma et al, 2004). pressure overload (e.g., hypertension or transverse aortic constriction), myocarditis or drug-induced cardiotoxicity, treatment with Gal-3 inhibitors such as N-acetyl-lactosamine, modified citrus pectin (MCP), or galactomannan polysaccharide attenuated cardiovascular inflammation and fibrosis (Arrieta et al, 2017;Calvier et al, 2015;Jaquenod De Giusti et al, 2015;Lopez et al, 2015;Martinez-Martinez, Lopez-Andres, et al, 2015;Martinez-Martinez, Calvier, et al, 2015;Sharma et al, 2004Sharma et al, , 2008Yu et al, 2013). In a sheep model of rapid pacing-induced AF, atrial levels of both TGF-β1 and Gal-3 were significantly elevated, which was reversed by treatment with the Gal-3 inhibitor GM-CT-01 (Takemoto et al, 2016).…”

Section: In Heart Diseasementioning

confidence: 99%

“…By using Gal-3 KO mice subjected to a variety of diseases, a number of studies have reported cardiovascular benefits by Gal-3 gene deletion (Table 2). In some disease models, cardiovascular benefits, measured as reduced severity in cardiac fibrosis, inflammation, or dysfunction, appear to be greater after Gal-3 gene deletion than that after treatment with Gal-3 inhibitors (Calvier et al, 2013;Jaquenod De Giusti et al, 2015;Nguyen et al, 2019; Table 2). The only exception is MI, in which Gal-3 KO mice suffered from more severe ventricular remodelling and a higher mortality due to insufficient inflammation and fibrotic healing (Gonzalez et al, 2014; Table 2).…”

Section: Experimental Evidence For Cardiovascular Benefits By Supprmentioning

confidence: 99%

“…The pro-fibrotic role of Gal-3 has been indicated by an increasing number of studies in vitro and in vivo. By inhibiting Gal-3 with genetic or pharmacological means, preclinical studies have shown cardiac benefits (Arrieta et al, 2017;Calvier et al, 2013;Jaquenod De Giusti, Ure, Rivadeneyra, Schattner, & Gomez, 2015;Yu et al, 2013). Clinical studies have reported high circulating levels of Gal-3 in patients with heart failure (HF), myocardial infarction (MI), or atrial fibrillation (AF; de Boer et al, 2011;Gurses et al, 2015;Kornej et al, 2015;Wu, Su, et al, 2015).…”

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confidence: 99%

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β‐Adrenoceptor activation affects galectin‐3 as a biomarker and therapeutic target in heart disease

Zhao

Nguyen

et al. 2019

British J Pharmacology

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Myocardial fibrosis is a key histopathological component that drives the progression of heart disease leading to heart failure and constitutes a therapeutic target. Recent preclinical and clinical studies have implicated galectin‐3 (Gal‐3) as a pro‐fibrotic molecule and a biomarker of heart disease and fibrosis. However, our knowledge is poor on the mechanism(s) that determine the blood level or regulate cardiac expression of Gal‐3. Recent studies have demonstrated that enhanced β‐adrenoceptor activity is a determinant of both circulating concentration and cardiac expression of Gal‐3. Pharmacological or transgenic activation of β‐adrenoceptors leads to increased blood levels of Gal‐3 and up‐regulated cardiac Gal‐3 expression, effect that can be reversed with the use of β‐adrenoceptor antagonists. Conversely, Gal‐3 gene deletion confers protection against isoprenaline‐induced cardiotoxicity and fibrogenesis. At the transcription level, β‐adrenoceptor stimulation activates cardiac mammalian sterile‐20‐like kinase 1, a pivotal kinase of the Hippo signalling pathway, which is associated with Gal‐3 up‐regulation. Recent studies have suggested a role for the β‐adrenoceptor‐Hippo signalling pathway in the regulation of cardiac Gal‐3 expression thereby contributing to the onset and progression of heart disease. This implies a therapeutic potential of the suppression of Gal‐3 expression. In this review, we discuss the effects of β‐adrenoceptor activity on Gal‐3 as a biomarker and causative mediator in the setting of heart disease and point out pivotal knowledge gaps. Linked Articles This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc

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Section: In Heart Diseasementioning

confidence: 99%

Section: In Heart Diseasementioning

confidence: 99%

Section: Experimental Evidence For Cardiovascular Benefits By Supprmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

β‐Adrenoceptor activation affects galectin‐3 as a biomarker and therapeutic target in heart disease

Zhao

Nguyen

et al. 2019

British J Pharmacology

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“…However, inflammatory cytokines can be expressed on the one hand due to the infiltration of inflammatory cells and on the other hand due to activation of resident cardiac cells triggered by viral infection [10, 16–18]. Importantly, viral infection of resident cardiac cells (especially cardiomyocytes and fibroblasts) and of inflammatory cells is well documented [8, 9, 15, 16, 19–22].…”

Section: Introductionmentioning

confidence: 99%

Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

Becher¹,

Gotzhein

Klingel

et al. 2017

Journal of Immunology Research

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Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

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Cardiac Fibrosis and Arrhythmogenesis

Nguyen

Kiriazis

Gao

et al. 2017

Comprehensive Physiology

103

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Myocardial injury, mechanical stress, neurohormonal activation, inflammation, and/or aging all lead to cardiac remodeling, which is responsible for cardiac dysfunction and arrhythmogenesis. Of the key histological components of cardiac remodeling, fibrosis either in the form of interstitial, patchy, or dense scars, constitutes a key histological substrate of arrhythmias. Here we discuss current research findings focusing on the role of fibrosis, in arrhythmogenesis. Numerous studies have convincingly shown that patchy or interstitial fibrosis interferes with myocardial electrophysiology by slowing down action potential propagation, initiating reentry, promoting after-depolarizations, and increasing ectopic automaticity. Meanwhile, there has been increasing appreciation of direct involvement of myofibroblasts, the activated form of fibroblasts, in arrhythmogenesis. Myofibroblasts undergo phenotypic changes with expression of gap-junctions and ion channels thereby forming direct electrical coupling with cardiomyocytes, which potentially results in profound disturbances of electrophysiology. There is strong evidence that systemic and regional inflammatory processes contribute to fibrogenesis (i.e., structural remodeling) and dysfunction of ion channels and Ca2+ homeostasis (i.e., electrical remodeling). Recognizing the pivotal role of fibrosis in the arrhythmogenesis has promoted clinical research on characterizing fibrosis by means of cardiac imaging or fibrosis biomarkers for clinical stratification of patients at higher risk of lethal arrhythmia, as well as preclinical research on the development of antifibrotic therapies. At the end of this review, we discuss remaining key questions in this area and propose new research approaches. © 2017 American Physiological Society. Compr Physiol 7:1009-1049, 2017.

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Macrophages and galectin 3 play critical roles in CVB3-induced murine acute myocarditis and chronic fibrosis

Cited by 65 publications

References 59 publications

β‐Adrenoceptor activation affects galectin‐3 as a biomarker and therapeutic target in heart disease

β‐Adrenoceptor activation affects galectin‐3 as a biomarker and therapeutic target in heart disease

Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

Cardiac Fibrosis and Arrhythmogenesis

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