Time-course analysis of cardiac and serum galectin-3 in viral myocarditis after an encephalomyocarditis virus inoculation

Noguchi, Kei; Tomita, Hiroyuki; Kanayama, Tomohiro; Niwa, Ayumi; Hatano, Yuichiro; Hoshi, Masato; Sugie, Shigeyuki; Okada, Hideshi; Niwa, Masayuki; Hara, Akira

doi:10.1371/journal.pone.0210971

Cited by 21 publications

(27 citation statements)

References 33 publications

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“…Recently, Gal-3 has been indicated to be involved in the following broad pathological processes: Inflammation [9], fibrosis, cell-to-cell [10,11] or cell-to-matrix [12] contacts, cell proliferation [13,14], and protection from apoptosis [15,16]. Furthermore, many studies have revealed that Gal-3 expression is detected in many disease conditions, such as heart disease [17][18][19][20][21][22][23], kidney disease [24][25][26][27], diabetes mellitus [24,25,28], viral infection [29][30][31][32], autoimmune disease [33][34][35][36], neurodegenerative disorders [37][38][39][40][41][42], and tumor formation [43][44][45][46][47][48][49][50][51][52].…”

Section: Clinical Significance and Applications Of Galectine-3 (Gal-3)mentioning

confidence: 99%

“…Gal-3 has been validated as a biomarker of fibrotic degeneration in acute myocarditis following cardiac viral infection. In an animal model of heart failure, serum Gal-3 levels was shown to be used as an diagnostic biomarker for early detection of cardiac degeneration in acute myocarditis [31] and acute myocardial infarction [56]. Furthermore, Gal-3 is also a good specific marker for indicating the early stage of glioma tumorigenesis [43].…”

Section: Clinical Significance and Applications Of Galectine-3 (Gal-3)mentioning

confidence: 99%

“…Serum levels of Gal-3 are usually determined by enzyme-linked immunosorbent assay (ELISA) using commercially available materials [57,58]. The localization or time-course of Gal-3 expression in various organs are examined immunohistochemically using commercially available anti-Gal-3 antibodies [31]. Gal-3 levels may be changed by different clinical factors in patients, depending on the underlying pathological conditions.…”

Section: Clinical Significance and Applications Of Galectine-3 (Gal-3)mentioning

confidence: 99%

“…A rat model of right ventricular heart failure, created by banding of the pulmonary artery, demonstrated that Gal-3 was significantly increased in both right and left ventricles and that protein kinase C promoted cardiac fibrosis and heart failure by modulating Gal-3 expression [82]. In order to clarify the important role of myocardial Gal-3 expression during the early stage of heart failure, the time-course analysis of cardiac and serum Gal-3 in viral myocarditis, which was induced at 12, 24, 48, 96 h, 7 and 10 days after specific virus-inoculation, was performed using an animal model [31]. Gal-3 was indicated as a useful histological biomarker of cardiac fibrosis in acute myocarditis following viral infection and serum Gal-3 levels might be an early diagnostic method for detecting cardiac fibrotic degeneration in acute myocarditis [31].…”

Section: Usefulness Of Gal-3 In Animal Modelsmentioning

confidence: 99%

“…In order to clarify the important role of myocardial Gal-3 expression during the early stage of heart failure, the time-course analysis of cardiac and serum Gal-3 in viral myocarditis, which was induced at 12, 24, 48, 96 h, 7 and 10 days after specific virus-inoculation, was performed using an animal model [31]. Gal-3 was indicated as a useful histological biomarker of cardiac fibrosis in acute myocarditis following viral infection and serum Gal-3 levels might be an early diagnostic method for detecting cardiac fibrotic degeneration in acute myocarditis [31].…”

Section: Usefulness Of Gal-3 In Animal Modelsmentioning

confidence: 99%

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Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

et al. 2020

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Galectin-3 is a β-galactoside-binding lectin which is important in numerous biological activities in various organs, including cell proliferation, apoptotic regulation, inflammation, fibrosis, and host defense. Galectin-3 is predominantly located in the cytoplasm and expressed on the cell surface, and then often secreted into biological fluids, like serum and urine. It is also released from injured cells and inflammatory cells under various pathological conditions. Many studies have revealed that galectin-3 plays an important role as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease, viral infection, autoimmune disease, neurodegenerative disorders, and tumor formation. In particular, it has been recognized that galectin-3 is extremely useful for detecting many of these diseases in their early stages. The purpose of this article is to review and summarize the recent literature focusing on the biomarker characteristics and long-term outcome predictions of galectin-3, in not only patients with various types of diseases, but associated animal models.

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Section: Clinical Significance and Applications Of Galectine-3 (Gal-3)mentioning

confidence: 99%

Section: Clinical Significance and Applications Of Galectine-3 (Gal-3)mentioning

confidence: 99%

Section: Clinical Significance and Applications Of Galectine-3 (Gal-3)mentioning

confidence: 99%

Section: Usefulness Of Gal-3 In Animal Modelsmentioning

confidence: 99%

Section: Usefulness Of Gal-3 In Animal Modelsmentioning

confidence: 99%

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Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

et al. 2020

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Modulation of the acute defence reaction by eplerenone prevents cardiac disease progression in viral myocarditis

et al. 2020

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Aims Left ventricular (LV) dysfunction in viral myocarditis is attributed to myocardial inflammation and fibrosis, inducing acute and long-time cardiac damage. Interventions are not established. On the basis of the link between inflammation, fibrosis, aldosterone, and extracellular matrix regulation, we aimed to investigate the effect of an early intervention with the mineralocorticoid receptor antagonist (MRA) eplerenone on cardiac remodelling in a murine model of persistent coxsackievirus B3 (CVB3)-induced myocarditis. Methods and results SWR/J mice were infected with 5 × 10 4 plaque-forming units of CVB3 (Nancy strain) and daily treated either with eplerenone (200 mg/kg body weight) or with placebo starting from Day 1. At Day 8 or 28 post infection, mice were haemodynamically characterized and subsequently sacrificed for immunohistological and molecular biology analyses. Eplerenone did not influence CVB3 load. Already at Day 8, 1.8-fold (P < 0.05), 1.4-fold (P < 0.05), 3.2-fold (P < 0.01), and 2.1-fold (P < 0.001) reduction in LV intercellular adhesion molecule 1 expression, presence of monocytes/macrophages, oxidative stress, and apoptosis, respectively, was observed in eplerenone-treated vs. untreated CVB3-infected mice. In vitro, eplerenone led to 1.4-fold (P < 0.01) and 1.2-fold (P < 0.01) less CVB3-induced cardiomyocyte oxidative stress and apoptosis. Furthermore, collagen production was 1.1-fold (P < 0.05) decreased in cardiac fibroblasts cultured with medium of eplerenone-treated vs. untreated CVB3-infected HL-1 cardiomyocytes. These ameliorations were in vivo translated into prevention of cardiac fibrosis, as shown by 1.4-fold (P < 0.01) and 2.1-fold (P < 0.001) lower collagen content in the LV of eplerenone-treated vs. untreated CVB3-infected mice at Days 8 and 28, respectively. This resulted in an early and long-lasting improvement of LV dimension and function, as indicated by reduced LV end-systolic volume and end-diastolic volume, and an increase in LV contractility (dP/dt max) and LV relaxation (dP/dt min), respectively (P < 0.05). Conclusions Early intervention with the MRA eplerenone modulates the acute host and defence reaction and prevents cardiac disease progression in experimental CVB3-induced myocarditis without aggravation of viral load. The findings advocate for an initiation of therapy of viral myocarditis as early as possible, even before the onset of inflammation-induced myocardial dysfunction. This may also have implications for coronavirus disease-19 therapy.

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Safety and pharmacokinetics of GB1211, an oral galectin-3 inhibitor: a single- and multiple-dose first-in-human study in healthy participants

Aslanis

Slack

MacKinnon

et al. 2023

Cancer Chemother Pharmacol

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Purpose Galectin-3, a β-galactoside-binding lectin, plays a key role in several cellular pathways involved in chronic inflammation, heart disease and cancer. GB1211 is an orally bioavailable galectin-3 inhibitor, developed to be systemically active. We report safety and pharmacokinetics (PK) of GB1211 in healthy participants. Methods This phase 1, double-blind, placebo-controlled, first-in-human study (NCT03809052) included a single ascending-dose phase (with a food-effect cohort) where participants across seven sequential cohorts were randomized 3:1 to receive oral GB1211 (5, 20, 50, 100, 200 or 400 mg) or placebo. In the multiple ascending-dose phase, participants received 50 or 100 mg GB1211 or placebo twice daily for 10 days. All doses were administered in the fasted state except in the food-effect cohort where doses were given 30 min after a high-fat meal. Results All 78 participants received at least one GB1211 dose (n = 58) or placebo (n = 20) and completed the study. No safety concerns were identified. Following single and multiple oral doses under fasted conditions, maximum GB1211 plasma concentrations were reached at 1.75–4 h (median) post-dose; mean half-life was 11–16 h. There was a ~ twofold GB1211 accumulation in plasma with multiple dosing, with steady-state reached within 3 days; 30% of the administered dose was excreted in urine as unchanged drug. Absorption in the fed state was delayed by 2 h but systemic exposure was unaffected. Conclusion GB1211 was well tolerated, rapidly absorbed, and displayed favorable PK, indicating a potential to treat multiple disease types. These findings support further clinical development of GB1211. Clinical trial registration The study was registered with ClinicalTrials.gov (identifier: NCT03809052).

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Time-course analysis of cardiac and serum galectin-3 in viral myocarditis after an encephalomyocarditis virus inoculation

Cited by 21 publications

References 33 publications

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

Modulation of the acute defence reaction by eplerenone prevents cardiac disease progression in viral myocarditis

Safety and pharmacokinetics of GB1211, an oral galectin-3 inhibitor: a single- and multiple-dose first-in-human study in healthy participants

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