A New Mouse Model of Chronic Myocarditis Induced by Recombinant Bacille Calmette–Guèrin Expressing a T-Cell Epitope of Cardiac Myosin Heavy Chain-α

Tajiri, Kazuko; Imanaka‐Yoshida, Kyoko; Tsujimura, Yusuke; Matsuo, Kazuhiro; Hiroe, Michiaki; Aonuma, Kazutaka; Ieda, Masaki; Yasutomi, Yasuhiro

doi:10.3390/ijms22020794

Cited by 6 publications

(5 citation statements)

References 38 publications

(47 reference statements)

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“…Although the mechanisms underlying the transition from acute to chronic inflammation currently remain unclear, TNC may play a role in the persistence of inflammation [ 75 ]. The expression of TNC has been detected in a mouse model of chronic myocarditis induced by recombinant Bacille Calmette-Guérin (BCG) expressing a cardiac autoantigen [ 150 ] as well as in endomyocardial biopsy specimens from patients with chronic myocarditis [ 151 ]. Prolonged inflammation in chronic myocarditis induces progressive tissue destruction, eventually resulting in the clinical phenotypes of DCM with severe heart failure.…”

Section: Myocarditismentioning

confidence: 99%

Tenascin-C in Heart Diseases—The Role of Inflammation

Imanaka‐Yoshida

2021

IJMS

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Tenascin-C (TNC) is a large extracellular matrix (ECM) glycoprotein and an original member of the matricellular protein family. TNC is transiently expressed in the heart during embryonic development, but is rarely detected in normal adults; however, its expression is strongly up-regulated with inflammation. Although neither TNC-knockout nor -overexpressing mice show a distinct phenotype, disease models using genetically engineered mice combined with in vitro experiments have revealed multiple significant roles for TNC in responses to injury and myocardial repair, particularly in the regulation of inflammation. In most cases, TNC appears to deteriorate adverse ventricular remodeling by aggravating inflammation/fibrosis. Furthermore, accumulating clinical evidence has shown that high TNC levels predict adverse ventricular remodeling and a poor prognosis in patients with various heart diseases. Since the importance of inflammation has attracted attention in the pathophysiology of heart diseases, this review will focus on the roles of TNC in various types of inflammatory reactions, such as myocardial infarction, hypertensive fibrosis, myocarditis caused by viral infection or autoimmunity, and dilated cardiomyopathy. The utility of TNC as a biomarker for the stratification of myocardial disease conditions and the selection of appropriate therapies will also be discussed from a clinical viewpoint.

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Section: Myocarditismentioning

confidence: 99%

Tenascin-C in Heart Diseases—The Role of Inflammation

Imanaka‐Yoshida

2021

IJMS

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“…The DCM is a heterogeneous group of myocardial diseases ( 18 ). The diagnosis of DCM is still performed by measuring the size of the left ventricle and the left ventricular ejection fraction through echocardiography ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

The Potential of Metabolism-Related Gene OGDHL as a Biomarker for Myocardial Remodeling in Dilated Cardiomyopathy

Tang

Zhu

Lü

et al. 2022

Front. Cardiovasc. Med.

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The development of dilated cardiomyopathy (DCM) is accompanied by a series of metabolic disorders, resulting in myocardial remodeling or exacerbation, while the mechanism remains not completely clear. This study was to find out the key metabolism-related genes involved in the onset of DCM, providing new insight into the pathogenesis of this disease. The datasets of GSE57338, GSE116250, and GSE5406 associated with hearts of patients with DCM were downloaded from the Gene Expression Omnibus database. GSE57338 was analyzed to screen out metabolism-related differentially expressed genes (DEGs), while GSE116250 and GSE5406 were utilized to verify the optimal genes through R software. Support vector machine recursive feature elimination algorithm and least absolute shrinkage and selection operator algorithm were used to determine key genes. Finally, 6 of 39 metabolism-related DEGs were screened out and identified as the optimal genes. After quantitative reverse-transcription polymerase chain reaction (qRT-PCR) validation performed on the samples drawn from the left ventricles of human hearts, it showed that only the expression of oxoglutarate dehydrogenase-like (OGDHL) increased while PLA2G2 decreased significantly in patients with DCM compared with non-failing donors, respectively. Furthermore, the higher OGDHL protein expression, except the change of PLA2G2, was also found in DCM hearts, and its mRNA expression was negatively correlated with myocardial Masson’s scores (r = –0.84, P = 0.009) and left ventricular end-diastolic diameter (LVEDd; r = –0.82, P = 0.014), which might be regulated by miR-3925-5p through further bioinformatics prediction and qRT-PCR verification. The data then suggested that the metabolism-related gene OGDHL was associated with myocardial fibrosis of DCM and probably a biomarker for myocardial remodeling in patients with DCM.

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“…This is a characteristic of the progressive accumulation of fibrotic tissues in the myocardium, which dilates the ventricles and impair cardiac function (12), in a manner that is equivalent to the second stage of myocarditis. This EAM mouse model is frequently used to study the different stages of myocarditis pathogenesis (13).…”

Section: Combination Of Sophora Flavescens Alkaloids and Panax Quinqu...mentioning

confidence: 99%

Combination ofSophora flavescensalkaloids and Panax quinquefolium saponins modulates different stages of experimental autoimmune myocarditis via the NF‑κB and TGF‑β1 pathways

Liu

Lin

et al. 2022

Exp Ther Med

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Chronic cardiac inflammation and fibrosis can progress into severe forms of cardiomyopathy. Sophora flavescens alkaloids (KuShen) have been previously reported to exert anti-inflammatory effects, whereas Panax quinquefolium saponins (XiYangShen) has been shown to alleviate cardiac fibrosis. Therefore, the potential effects of their combination (KX) on different stages of autoimmune myocarditis were investigated in the present study. Mice were randomly divided into the following four groups: Control; experimental autoimmune myocarditis (EAM); KX-High (275 mg/kg); and KX-Low (138 mg/kg). A 21-day and a 60-day EAM model was established through multi-site subcutaneous injections of cardiac myosin mixed with complete Freund's adjuvant on days 0, 7, 21 and 42. Mice in the High and Low KX groups were treated by gavage (10 ml/kg) daily from day 0 (1 day before treatment) until sacrifice (day 21 or 60). Mice in the control and EAM groups received an equivalent volume of distilled water. The levels of lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTn-I), IL-1β, IL-6, TNF-α, TGF-β1, collagen type I (Col Ⅰ) and collagen type III (Col Ⅲ) were measured by ELISA in the mouse myocardial tissues or serum. Myocardial tissue structure and extent of fibrosis were visualized using H&E and Masson's staining. Western blotting and immunohistochemistry were used to measure the expression levels NF-κB and TGF-β1 pathway proteins in the myocardial tissues. The degree of inflammation in the 21-day EAM model was found to be significantly higher compared with that in the 60-day EAM model. KX significantly reduced the inflammatory response at 21 days by decreasing the expression levels of CK-MB, LDH, cTn-I, IL-1β, IL-6, TNF-α and TGF-β-activated kinase 1-binding protein 1/NF-κB pathway proteins. Myocardial fibrosis in the 60-day EAM model was also significantly worse compared with that in the 21-day EAM model. However, fibrosis was significantly delayed by treatment with KX. In addition, KX significantly decreased the expression levels of TGF-β1, Smad2, Smad4, Col I and Col III. Therefore, these data suggest that KX is beneficial for treating myocarditis by targeting multiple pathways.

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A New Mouse Model of Chronic Myocarditis Induced by Recombinant Bacille Calmette–Guèrin Expressing a T-Cell Epitope of Cardiac Myosin Heavy Chain-α

Cited by 6 publications

References 38 publications

Tenascin-C in Heart Diseases—The Role of Inflammation

Tenascin-C in Heart Diseases—The Role of Inflammation

The Potential of Metabolism-Related Gene OGDHL as a Biomarker for Myocardial Remodeling in Dilated Cardiomyopathy

Combination ofSophora flavescensalkaloids and Panax quinquefolium saponins modulates different stages of experimental autoimmune myocarditis via the NF‑κB and TGF‑β1 pathways

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