Beneficial Effects of Low-Dose Benidipine in Acute Autoimmune Myocarditis-Suppressive Effects on Inflammatory Cytokines and Inducible Nitric Oxide Synthase-

Yuan, Zuyi; Kishimoto, Chiharu; Shioji, Kosei

doi:10.1253/circj.67.545

Cited by 31 publications

(7 citation statements)

References 36 publications

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“…with interferons) are emerging [3]. In our lab, we have focused on the suppression of inflammation during the course of myocarditis, and demonstrated beneficial effects of low-dose benidipine, L -arginine and peroxisome proliferator-activated receptor-γ ligands in myocarditis rats, respectively [18,19,20]. …”

Section: Discussionmentioning

confidence: 99%

“…According to our previous research [18], macroscopic pathological findings were graded as previously described on a scale of 0-4 as follows: 0 (normal appearance), 1 (focal discolored area), 2 (multiple or diffuse discolored areas and not exceeding one third of the heart), 3 (diffuse discolored areas not exceeding two thirds of the heart) and 4 (diffuse discolored areas exceeding two thirds of the heart). After macroscopic examination, the hearts were transversely sliced.…”

Section: Methodsmentioning

confidence: 99%

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miR-590-3p Is a Novel MicroRNA in Myocarditis by Targeting Nuclear Factor Kappa-B in vivo

et al. 2015

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Objective: Nuclear factor kappa-B (NF-κB)-induced inflammation leads to myocarditis and heart dysfunction. How microRNAs (miRNAs) contribute to this process is poorly defined. The aim of this study was to investigate whether miRNAs regulate NF-κB-induced inflammation in experimental autoimmune myocarditis (EAM) in vivo. Methods and Results: NF-κB and its related proinflammatory genes, including interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a), were activated in EAM. Profiling of NF-κB-related miRNAs revealed that miR-590-3p was strikingly reduced in EAM. We found IL-6-induced proinflammatory signaling via miR-590-3p reduction, p50 induction, NF-κB activation and IL-6/TNF-a expression. Moreover, a luciferase reporter assay demonstrated that miR-590-3p directly interacted with the 3' UTR (untranslated region) of the p50 subunit, and that miR-590-3p overexpression inhibited p50 expression. Finally, miR-590-3p transfection through adeno-associated virus significantly inhibited p50 expression, suppressed NF-κB activity and blocked IL-6/TNF-a expression in vivo, reducing the lesion area and improving cardiac function in EAM. Conclusion: miR-590-3p is a novel NF-κB-related miRNA that directly targets the p50 subunit. This may provide a novel strategy for the treatment of myocarditis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

miR-590-3p Is a Novel MicroRNA in Myocarditis by Targeting Nuclear Factor Kappa-B in vivo

et al. 2015

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“…Margulies and colleagues discovered a biomarker that predicts recovery from HF 37 , and Deng and co-workers developed a molecular signature which detects early cardiac transplant rejection 34 that has now entered the clinic 21 . Our discoveries reported here are clinically relevant as high diagnostic sensitivity in cardiomyopathy facilitates the appropriate use of new myocarditis specific therapies 2, 3, 12-15, 38-42 . Early and accurate diagnosis in this condition is essential so as to avoid excessive myocardial damage resulting from failure to apply therapies.…”

Section: Discussionmentioning

confidence: 74%

“…Early and accurate diagnosis in this condition is essential so as to avoid excessive myocardial damage resulting from failure to apply therapies. New candidate therapies for myocarditis include anti-inflammatory cytokines 42 , anti-viral agents, and immunoabsorption 2, 3, 12-15, 38-42 . In this regard, IFN B therapy has been safely applied in humans, leading to increased LV function and elimination of viral infection 13 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Biomarkers for the Accurate Diagnosis of Myocarditis

et al. 2011

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Background Lymphocytic myocarditis is a clinically important condition that is difficult to diagnose and distinguish. We hypothesized that the transcriptome obtained from an endomyocardial biopsy (EMB) would yield clinically relevant and accurate molecular signatures. Methods and results Microarray analysis was performed on samples from patients with histologically proven lymphocytic myocarditis (n=16) and idiopathic dilated cardiomyopathy (IDCM, n=32) to develop accurate diagnostic transcriptome-based biomarkers (TBB) using multiple classification algorithms. We identified 9,878 genes differentially expressed in lymphocytic myocarditis vs. IDCM (FC>1.2, FDR<5%), from which a TBB containing 62 genes was identified, which distinguished myocarditis with 100% sensitivity (95% CI: 46-100%) and 100% specificity (95% CI: 66-100%) and which was generalizable to a broad range of secondary cardiomyopathies associated with inflammation (n=27), ischemic cardiomyopathy (n=8) and the normal heart (n=11). Multiple classification algorithms and quantitative realtime RT-PCR analysis further reduced this subset to a highly robust molecular signature of 13 genes, which still performed with 100% accuracy. Conclusions Together these findings demonstrate that transcriptomic biomarkers from a single EMB can improve the clinical detection of patients with inflammatory diseases of the heart. This approach advances the clinical management and treatment of cardiac disorders with highly variable outcome.

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“…21 The nasal administration of CM and treatment with CM-coupled splenocytes were done in A/J mice with EAM, driven by IL-4-secreting Th2 Fig 6. CD8 + T cells are not involved in active EAM induction or the suppressive effect of mPEG-CM treatment.…”

Section: Discussionmentioning

confidence: 99%

Monomethoxypolyethylene Glycol-Modified Cardiac Myosin Treatment Blocks the Active and Passive Induction of Experimental Autoimmune Myocarditis

Hamada

Takata

Kiyoku

et al. 2004

Circ J

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Beneficial Effects of Low-Dose Benidipine in Acute Autoimmune Myocarditis-Suppressive Effects on Inflammatory Cytokines and Inducible Nitric Oxide Synthase-

Cited by 31 publications

References 36 publications

miR-590-3p Is a Novel MicroRNA in Myocarditis by Targeting Nuclear Factor Kappa-B in vivo

miR-590-3p Is a Novel MicroRNA in Myocarditis by Targeting Nuclear Factor Kappa-B in vivo

Transcriptomic Biomarkers for the Accurate Diagnosis of Myocarditis

Monomethoxypolyethylene Glycol-Modified Cardiac Myosin Treatment Blocks the Active and Passive Induction of Experimental Autoimmune Myocarditis

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