The Experts below are selected from a list of 1683 Experts worldwide ranked by ideXlab platform
Taekyun Shin - One of the best experts on this subject based on the ideXlab platform.
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Immunohistochemical analysis of periostin in the hearts of Lewis rats with Experimental Autoimmune Myocarditis.
The Journal of veterinary medical science, 2020Co-Authors: Yuna Choi, Taekyun Shin, Meejung Ahn, Tae-young Kang, Jiyoon Chun, Jeong-tae KimAbstract:Periostin plays a critical role in tissue regeneration and homeostasis. The aim of this study was to evaluate the changes in periostin levels in the hearts of rats with Experimental Autoimmune Myocarditis (EAM). Western blot analysis revealed that the expression levels of periostin and alpha-smooth muscle actin were significantly increased at day 14 post-immunization. Immunohistochemical analysis indicated that periostin was expressed in macrophages and fibroblasts in the hearts of EAM-induced rats. In conclusion, these results suggest that increased periostin expression in macrophages and fibroblasts promotes cardiac fibrosis in EAM-induced rats, potentially by enhancing immune cell infiltration. Therefore, periostin should be further investigated as a candidate therapeutic target for Myocarditis.
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Increased expression of osteopontin in the heart tissue of Lewis rats with Experimental Autoimmune Myocarditis.
The Journal of veterinary medical science, 2006Co-Authors: Taekyun Shin, Meejung Ahn, Heechul Kim, Hyung-min Kim, Yoh MatsumotoAbstract:The expression of osteopontin (OPN) in the hearts of rats with Experimental Autoimmune Myocarditis (EAM) was evaluated. Western blot analysis showed that OPN was significantly increased in the hearts with EAM compared with those of complete Freund's adjuvant (CFA) immunized control. Immunohistochemically, OPN was weakly expressed in the cardiomyocytes in the heart with normal and CFA immunized controls. In EAM lesions, OPN was intensely immunostained in some inflammatory cells, mainly ED1 positive macrophages. These findings suggest that OPN is significantly increased in EAM lesions and that OPN mediates the inflammatory process in the course of rat EAM model.
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Increased expression of phospholipase D in the heart with Experimental Autoimmune Myocarditis in Lewis rats.
Immunological investigations, 2004Co-Authors: Meejung Ahn, Yoh Matsumoto, Yongduk Lee, Ki-bum Sim, Sik Min, Myung-bok Wie, Young-gyun Shin, Taekyun ShinAbstract:The expression of phospholipase D (PLD) in the hearts of rats with Experimental Autoimmune Myocarditis (EAM) was studied to elucidate the functional role of PLD in the pathogenesis of EAM. Western blot analysis showed that the level of the PLD1 isoform was significantly increased in the hearts of rats with EAM on days 14, 17 and 21 postimmunization (pi) (P < 0.01; control vs EAM at 14 pi, 17 pi and 21 pi). The phenotypes of cells exhibiting increased PLD1 expression were primarily inflammatory cells, including ED1 positive macrophages, in the inflammatory EAM lesions. Some cardiomyocytes also showed increased PLD1 immunoreaction in and around EAM lesions. Some PLD1-positive cells were also positive for proliferating cell nuclear antigen in some cardiomyocytes or terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling in some macrophages, suggesting that PLD1 positive cells have a capacity for proliferation or apoptosis depending on cell types in the target organ. Thus, it is postulated that increased expression of PLD1 in EAM may support an early inflammatory response in proliferating inflammatory cells, and its expression in cardiomyocytes may help them to survive by activation of survival factors in hearts with EAM.
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An inhibitor of inducible nitric oxide synthase ameliorates Experimental Autoimmune Myocarditis in Lewis rats.
Journal of Neuroimmunology, 1998Co-Authors: Taekyun Shin, Naoyuki Tanuma, Seung Joon Kim, Jae-kwang Jin, Changjong Moon, Ki Ok Kim, Kuniko Kohyama, Yoh Matsumoto, Byung Hwa HyunAbstract:We studied the effect of nitric oxide (NO) on Experimental Autoimmune Myocarditis (EAC) in rats. We examined the role of inducible nitric oxide synthase (iNOS), an enzyme that produces NO, on hearts affected with EAC, by testing the effects of aminoguanidine (AG), a selective iNOS inhibitor, on the course of EAC. Western blotting detected iNOS in the affected cardiac tissues, but not in CFA immunized cases. Immunohistochemically, the majority of ED1+ macrophages in the EAC lesions were positive for iNOS and nitrotyrosine. A high dose of AG (200 mg/kg/day) significantly reduced the incidence of EAC (p
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An inhibitor of inducible nitric oxide synthase ameliorates Experimental Autoimmune Myocarditis in Lewis rats.
Journal of neuroimmunology, 1998Co-Authors: Taekyun Shin, Naoyuki Tanuma, Changjong Moon, Kuniko Kohyama, Yoh Matsumoto, S Kim, J Jin, K Kim, B HyunAbstract:We studied the effect of nitric oxide (NO) on Experimental Autoimmune Myocarditis (EAC) in rats. We examined the role of inducible nitric oxide synthase (iNOS), an enzyme that produces NO, on hearts affected with EAC, by testing the effects of aminoguanidine (AG), a selective iNOS inhibitor, on the course of EAC. Western blotting detected iNOS in the affected cardiac tissues, but not in CFA immunized cases. Immunohistochemically, the majority of ED1+ macrophages in the EAC lesions were positive for iNOS and nitrotyrosine. A high dose of AG (200 mg/kg/day) significantly reduced the incidence of EAC (p < 0.05) and ameliorated the histological score for the cardiac inflammation (p < 0.01) compared with the low dose AG (100 mg/kg/day) and vehicle treated groups. The immunoblot analysis showed that a high dose of AG effectively suppressed iNOS in hearts affected with EAC. An iNOS band was barely detected in the high dose AG (200 mg/kg) treated group, while it was distinctively visualized in the vehicle and low dose AG (100 mg/kg) treated groups. These results suggest that iNOS is upregulated in EAC lesions and increased NO production plays an important role in the development of EAC. In addition, selective iNOS inhibitors may have a therapeutic role in treating certain Autoimmune diseases including EAC.
Przemyslaw Blyszczuk - One of the best experts on this subject based on the ideXlab platform.
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absence of nonhematopoietic mhc class ii expression protects mice from Experimental Autoimmune Myocarditis
European Journal of Immunology, 2016Co-Authors: Christoph Thelemann, Przemyslaw Blyszczuk, Urs Eriksson, Gabriela Kania, Sergio Haller, Muriel Rosa, Samuel Rotman, Walter Reith, Hans AchaorbeaAbstract:Experimental Autoimmune Myocarditis (EAM) is a CD4(+) T-cell-mediated model of human inflammatory dilated cardiomyopathies. Heart-specific CD4(+) T-cell activation is dependent on autoantigens presented by MHC class II (MHCII) molecules expressed on professional APCs. In this study, we addressed the role of inflammation-induced MHCII expression by cardiac nonhematopoietic cells on EAM development. EAM was induced in susceptible mice lacking inducible expression of MHCII molecules on all nonhematopoietic cells (pIV-/- K14 class II transactivator (CIITA) transgenic (Tg) mice) by immunization with α-myosin heavy chain peptide in CFA. Lack of inducible nonhematopoietic MHCII expression in pIV-/- K14 CIITA Tg mice conferred EAM resistance. In contrast, cardiac pathology was induced in WT and heterozygous mice, and correlated with elevated cardiac endothelial MHCII expression. Control mice with Myocarditis displayed an increase in infiltrating CD4(+) T cells and in expression of IFN-γ, which is the major driver of nonhematopoietic MHCII expression. Mechanistically, IFN-γ neutralization in WT mice shortly before disease onset resulted in reduced cardiac MHCII expression and pathology. These findings reveal a previously overlooked contribution of IFN-γ to induce endothelial MHCII expression in the heart and to progress cardiac pathology during Myocarditis.
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innate signaling promotes formation of regulatory nitric oxide producing dendritic cells limiting t cell expansion in Experimental Autoimmune Myocarditis
Circulation, 2013Co-Authors: Gabriela Kania, Urs Eriksson, Stefanie Siegert, Silvia Behnke, Rafael Pradosrosales, Arturo Casadevall, Thomas F Luscher, Sanjiv A Luther, Manfred Kopf, Przemyslaw BlyszczukAbstract:Background—Activation of innate pattern-recognition receptors promotes CD4+ T-cell–mediated Autoimmune Myocarditis and subsequent inflammatory cardiomyopathy. Mechanisms that counterregulate exaggerated heart-specific autoimmunity are poorly understood. Methods and Results—Experimental Autoimmune Myocarditis was induced in BALB/c mice by immunization with α-myosin heavy chain peptide and complete Freund’s adjuvant. Together with interferon-γ, heat-killed Mycobacterium tuberculosis, an essential component of complete Freund’s adjuvant, converted CD11bhiCD11c− monocytes into tumor necrosis factor-α– and nitric oxide synthase 2–producing dendritic cells (TipDCs). Heat-killed M. tuberculosis stimulated production of nitric oxide synthase 2 via Toll-like receptor 2–mediated nuclear factor-κB activation. TipDCs limited antigen-specific T-cell expansion through nitric oxide synthase 2–dependent nitric oxide production. Moreover, they promoted nitric oxide synthase 2 production in hematopoietic and stromal cells ...
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Heart-infiltrating prominin-1+/CD133+ progenitor cells represent the cellular source of transforming growth factor beta-mediated cardiac fibrosis in Experimental Autoimmune Myocarditis.
Circulation research, 2009Co-Authors: Gabriela Kania, Przemyslaw Blyszczuk, Alan Valaperti, Sokrates Stein, Davide Germano, Stephan Dirnhofer, Lukas Hunziker, Christian M. Matter, Urs ErikssonAbstract:Rationale: Myocardial fibrosis is a hallmark of inflammation-triggered end-stage heart disease, a common cause of heart failure in young patients. Objective: We used CD4+ T-cell–mediated Experimental Autoimmune Myocarditis model to determine the parameters regulating cardiac fibrosis in inflammatory heart disease. Methods and Results: α-Myosin heavy chain peptide/complete Freund’s adjuvant immunization was used to induce Experimental Autoimmune Myocarditis in BALB/c mice. Chimeric mice, reconstituted with enhanced green fluorescence protein (EGFP)+ bone marrow, were used to track the fate of inflammatory cells. Prominin-1+ cells were isolated from the inflamed hearts, cultured in vitro and injected intracardially at different stages of Experimental Autoimmune Myocarditis. Transforming growth factor (TGF)-β–mediated fibrosis was addressed using anti–TGF-β antibody treatment. Myocarditis peaked 21 days after immunization and numbers of cardiac fibroblasts progressively increased on follow-up. In chimeric mi...
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Future therapeutic strategies in inflammatory cardiomyopathy: insights from the Experimental Autoimmune Myocarditis model.
Cardiovascular & hematological disorders drug targets, 2008Co-Authors: Przemyslaw Blyszczuk, Alan Valaperti, Urs ErikssonAbstract:Inflammatory cardiomyopathy is a common cause of heart failure developing on a basis of cardiac inflammation. Cardiac inflammation - or Myocarditis - is usually triggered by infections or cardiac damage of any cause. Experimental Autoimmune Myocarditis refers to a CD4(+) T cell-mediated mouse model of inflammatory cardiomyopathy. So far, the Experimental Autoimmune Myocarditis model helped us to understand the role of various chemokines, cytokines, and cell subsets in the progression of inflammatory heart disease. Here, we review the current therapeutic options for inflammatory cardiomyopathy, and delineate potential future treatment approaches from the most recent mechanistic insights given by the Experimental Autoimmune Myocarditis model.
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cd11b monocytes abrogate th17 cd4 t cell mediated Experimental Autoimmune Myocarditis
Journal of Immunology, 2008Co-Authors: Alan Valaperti, Przemyslaw Blyszczuk, Gabriela Kania, Davide Germano, Rene R Marty, Nora Mauermann, Stefan Dirnhofer, Bernd M Leimenstoll, Chen Dong, Christian MuellerAbstract:Experimental Autoimmune Myocarditis (EAM) represents a Th17 T cell-mediated mouse model of postinflammatory heart disease. In BALB/c wild-type mice, EAM is a self-limiting disease, peaking 21 days after alpha-myosin H chain peptide (MyHC-alpha)/CFA immunization and largely resolving thereafter. In IFN-gammaR(-/-) mice, however, EAM is exacerbated and shows a chronic progressive disease course. We found that this progressive disease course paralleled persistently elevated IL-17 release from T cells infiltrating the hearts of IFN-gammaR(-/-) mice 30 days after immunization. In fact, IL-17 promoted the recruitment of CD11b(+) monocytes, the major heart-infiltrating cells in EAM. In turn, CD11b(+) monocytes suppressed MyHC-alpha-specific Th17 T cell responses IFN-gamma-dependently in vitro. In vivo, injection of IFN-gammaR(+/+)CD11b(+), but not IFN-gammaR(-/-)CD11b(+), monocytes, suppressed MyHC-alpha-specific T cells, and abrogated the progressive disease course in IFN-gammaR(-/-) mice. Finally, coinjection of MyHC-alpha-specific, but not OVA-transgenic, IFN-gamma-releasing CD4(+) Th1 T cell lines, together with MyHC-alpha-specific Th17 T cells protected RAG2(-/-) mice from EAM. In conclusion, CD11b(+) monocytes play a dual role in EAM: as a major cellular substrate of IL-17-induced inflammation and as mediators of an IFN-gamma-dependent negative feedback loop confining disease progression.
Yoh Matsumoto - One of the best experts on this subject based on the ideXlab platform.
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Anti-αβ T cell receptor antibody prevents the progression of Experimental Autoimmune Myocarditis
Clinical and experimental immunology, 2008Co-Authors: Haruo Hanawa, Tohru Izumi, Akira Shibata, Makoto Kodama, Takayuki Inomata, Yoh Matsumoto, M. Tuchida, Toru AboAbstract:We investigated the effects of anti-alpha beta T cell receptor antibody in rat Experimental Autoimmune Myocarditis (EAM), using a new animal model of Autoimmune Myocarditis characterized by the appearance of multinucleated giant cells. EAM was induced by injecting Lewis rats subcutaneously in the footpads with 1.0 mg of human cardiac myosin in an equal volume of Freund's complete adjuvant (FCA) on days 0 and 7. In experiment 1, we evaluated the effect of long-term anti-alpha beta TCR antibody therapy on prevention of progression of EAM. Long-term administration of anti-alpha beta TCR antibody prevented progression of EAM in a dose-dependent manner. Flow cytometry performed at the time of sacrifice showed that the percentage of alpha beta T cells in lymph nodes and spleen was similar in the control group and the group in which almost no histologic evidence of Myocarditis was found. In experiment 2, we examined the effects of short-term therapy. Rats were killed at different stages and pathologic specimens were examined. Short-term therapy delayed the onset of Myocarditis. Results of flow cytometry suggested that impairment of antigen recognition or T cell function by occupancy of the TCR rather than depletion of TCR was the mechanism responsible for suppression of EAM.
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Increased expression of osteopontin in the heart tissue of Lewis rats with Experimental Autoimmune Myocarditis.
The Journal of veterinary medical science, 2006Co-Authors: Taekyun Shin, Meejung Ahn, Heechul Kim, Hyung-min Kim, Yoh MatsumotoAbstract:The expression of osteopontin (OPN) in the hearts of rats with Experimental Autoimmune Myocarditis (EAM) was evaluated. Western blot analysis showed that OPN was significantly increased in the hearts with EAM compared with those of complete Freund's adjuvant (CFA) immunized control. Immunohistochemically, OPN was weakly expressed in the cardiomyocytes in the heart with normal and CFA immunized controls. In EAM lesions, OPN was intensely immunostained in some inflammatory cells, mainly ED1 positive macrophages. These findings suggest that OPN is significantly increased in EAM lesions and that OPN mediates the inflammatory process in the course of rat EAM model.
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Increased expression of phospholipase D in the heart with Experimental Autoimmune Myocarditis in Lewis rats.
Immunological investigations, 2004Co-Authors: Meejung Ahn, Yoh Matsumoto, Yongduk Lee, Ki-bum Sim, Sik Min, Myung-bok Wie, Young-gyun Shin, Taekyun ShinAbstract:The expression of phospholipase D (PLD) in the hearts of rats with Experimental Autoimmune Myocarditis (EAM) was studied to elucidate the functional role of PLD in the pathogenesis of EAM. Western blot analysis showed that the level of the PLD1 isoform was significantly increased in the hearts of rats with EAM on days 14, 17 and 21 postimmunization (pi) (P < 0.01; control vs EAM at 14 pi, 17 pi and 21 pi). The phenotypes of cells exhibiting increased PLD1 expression were primarily inflammatory cells, including ED1 positive macrophages, in the inflammatory EAM lesions. Some cardiomyocytes also showed increased PLD1 immunoreaction in and around EAM lesions. Some PLD1-positive cells were also positive for proliferating cell nuclear antigen in some cardiomyocytes or terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling in some macrophages, suggesting that PLD1 positive cells have a capacity for proliferation or apoptosis depending on cell types in the target organ. Thus, it is postulated that increased expression of PLD1 in EAM may support an early inflammatory response in proliferating inflammatory cells, and its expression in cardiomyocytes may help them to survive by activation of survival factors in hearts with EAM.
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An inhibitor of inducible nitric oxide synthase ameliorates Experimental Autoimmune Myocarditis in Lewis rats.
Journal of Neuroimmunology, 1998Co-Authors: Taekyun Shin, Naoyuki Tanuma, Seung Joon Kim, Jae-kwang Jin, Changjong Moon, Ki Ok Kim, Kuniko Kohyama, Yoh Matsumoto, Byung Hwa HyunAbstract:We studied the effect of nitric oxide (NO) on Experimental Autoimmune Myocarditis (EAC) in rats. We examined the role of inducible nitric oxide synthase (iNOS), an enzyme that produces NO, on hearts affected with EAC, by testing the effects of aminoguanidine (AG), a selective iNOS inhibitor, on the course of EAC. Western blotting detected iNOS in the affected cardiac tissues, but not in CFA immunized cases. Immunohistochemically, the majority of ED1+ macrophages in the EAC lesions were positive for iNOS and nitrotyrosine. A high dose of AG (200 mg/kg/day) significantly reduced the incidence of EAC (p
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An inhibitor of inducible nitric oxide synthase ameliorates Experimental Autoimmune Myocarditis in Lewis rats.
Journal of neuroimmunology, 1998Co-Authors: Taekyun Shin, Naoyuki Tanuma, Changjong Moon, Kuniko Kohyama, Yoh Matsumoto, S Kim, J Jin, K Kim, B HyunAbstract:We studied the effect of nitric oxide (NO) on Experimental Autoimmune Myocarditis (EAC) in rats. We examined the role of inducible nitric oxide synthase (iNOS), an enzyme that produces NO, on hearts affected with EAC, by testing the effects of aminoguanidine (AG), a selective iNOS inhibitor, on the course of EAC. Western blotting detected iNOS in the affected cardiac tissues, but not in CFA immunized cases. Immunohistochemically, the majority of ED1+ macrophages in the EAC lesions were positive for iNOS and nitrotyrosine. A high dose of AG (200 mg/kg/day) significantly reduced the incidence of EAC (p < 0.05) and ameliorated the histological score for the cardiac inflammation (p < 0.01) compared with the low dose AG (100 mg/kg/day) and vehicle treated groups. The immunoblot analysis showed that a high dose of AG effectively suppressed iNOS in hearts affected with EAC. An iNOS band was barely detected in the high dose AG (200 mg/kg) treated group, while it was distinctively visualized in the vehicle and low dose AG (100 mg/kg) treated groups. These results suggest that iNOS is upregulated in EAC lesions and increased NO production plays an important role in the development of EAC. In addition, selective iNOS inhibitors may have a therapeutic role in treating certain Autoimmune diseases including EAC.
Byung Hwa Hyun - One of the best experts on this subject based on the ideXlab platform.
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An inhibitor of inducible nitric oxide synthase ameliorates Experimental Autoimmune Myocarditis in Lewis rats.
Journal of Neuroimmunology, 1998Co-Authors: Taekyun Shin, Naoyuki Tanuma, Seung Joon Kim, Jae-kwang Jin, Changjong Moon, Ki Ok Kim, Kuniko Kohyama, Yoh Matsumoto, Byung Hwa HyunAbstract:We studied the effect of nitric oxide (NO) on Experimental Autoimmune Myocarditis (EAC) in rats. We examined the role of inducible nitric oxide synthase (iNOS), an enzyme that produces NO, on hearts affected with EAC, by testing the effects of aminoguanidine (AG), a selective iNOS inhibitor, on the course of EAC. Western blotting detected iNOS in the affected cardiac tissues, but not in CFA immunized cases. Immunohistochemically, the majority of ED1+ macrophages in the EAC lesions were positive for iNOS and nitrotyrosine. A high dose of AG (200 mg/kg/day) significantly reduced the incidence of EAC (p
Makoto Kodama - One of the best experts on this subject based on the ideXlab platform.
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Sulfated Polysaccharide Fucoidan Ameliorates Experimental Autoimmune Myocarditis in Rats
Journal of cardiovascular pharmacology and therapeutics, 2010Co-Authors: Komei Tanaka, Haruo Hanawa, Makoto Kodama, Masahiro Ito, Satoru Hirono, Wataru Mitsuma, Makoto Tomita, Shinpei Kimura, Makoto Hoyano, Yoshifusa AizawaAbstract:Homing of cardiac myosin-specific CD4-positive T cells into the myocardium is the initial pathologic event of Experimental Autoimmune Myocarditis (EAM). Subsequently, various bystander inflammatory cells are recruited into the myocardium crossing vascular endothelial cell walls. Sulfated polysaccharide fucoidan binds selectin nonselectively and blocks its function. Therefore, this study was designed to evaluate whether in vivo fucoidan treatment can improve EAM. A 21-day infusion of physiological saline or fucoidan was administrated intraperitoneally to the rats with sham operation (sham-saline, n = 5; sham-fucoidan, n = 6) or those with cardiac myosin injection (EAM-saline, n = 10; EAM-fucoidan, n = 10). After 3 weeks, fucoidan treatment improved left ventricular ejection fraction (79.04 ± 2.81 vs 65.94% ± 3.22%; P < .01 vs EAM-saline) with a reduced ratio of heart weight to body weight (4.016 ± 0.239 vs 4.975 ± 0.252 mg/g; P < .05 vs EAM-saline) in EAM. Furthermore, fucoidan treatment decreased serum levels of BNP (292.0 ± 53.4 vs 507.4 ± 89.2 ng/mL; P < .05 vs EAM-saline) and the Myocarditis area (31.66 ± 1.53 vs 42.51% ± 3.24%; P < .01 vs EAM-saline) in EAM. These beneficial effects of fucoidan were accompanied by inhibition of both macrophage and CD4-positive T-cell infiltration into the myocardium. Fucoidan, a nonselective selectin blocker, attenuates the progression of EAM. This observation may be explained, at least in part, by blocking the extravasation of inflammatory cells into the myocardium.
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Telmisartan ameliorates Experimental Autoimmune Myocarditis associated with inhibition of inflammation and oxidative stress.
European journal of pharmacology, 2010Co-Authors: Vijayakumar Sukumaran, Makoto Kodama, Kenichi Watanabe, Punniyakoti T Veeraveedu, Narasimman Gurusamy, Varatharajan Rajavel, Kenji Suzuki, Ken'ichi Yamaguchi, Yoshifusa AizawaAbstract:Excess cytokine produced by inflammatory stimuli contributes to the progression of myocardial damage in Myocarditis. Angiotensin-II has been shown to play a pivotal role in the pathophysiology of various organs, especially the cardiovascular system. Some angiotensin II type 1 receptor antagonists are reported to inhibit proinflammatory cytokine production in vitro and in vivo. We investigated whether telmisartan, an angiotensin II type 1 receptor antagonist protects against Experimental Autoimmune Myocarditis by suppression of inflammatory cytokines and oxidative stress. Experimental Autoimmune Myocarditis was induced in Lewis rats by immunization with porcine cardiac myosin. The rats were divided into two groups and treated with either telmisartan (10mg/kg/day) or vehicle for 21days. Age-matched normal rats without immunization were also included in this study. Myocardial functional parameters were significantly improved by treatment with telmisartan compared with vehicle-treated rats. Increased myocardial mRNA expressions of inflammatory cytokines [interleukin (IL-6), IL-1β, tumor necrosis factor-α and interferon-γ] were also suppressed by telmisartan treatment compared with vehicle-treated rats. Myocardial protein expressions of NADPH oxidase subunits p47phox, Nox-4, and gp91phox, myocardial levels of 8-hydroxydeoxyguanosine and 4-hydroxy-2-nonenal, and myocardial apoptosis were also significantly decreased by telmisartan treatment compared with vehicle-treated rats. Further, telmisartan significantly decreased endoplasmic reticulum stress markers in Experimental Autoimmune Myocarditis rats. These findings suggest that telmisartan protects against Experimental Autoimmune Myocarditis in rats, at least in part by suppressing inflammatory cytokines and oxidative stress; however, further investigations are needed before clinical use.
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Anti-αβ T cell receptor antibody prevents the progression of Experimental Autoimmune Myocarditis
Clinical and experimental immunology, 2008Co-Authors: Haruo Hanawa, Tohru Izumi, Akira Shibata, Makoto Kodama, Takayuki Inomata, Yoh Matsumoto, M. Tuchida, Toru AboAbstract:We investigated the effects of anti-alpha beta T cell receptor antibody in rat Experimental Autoimmune Myocarditis (EAM), using a new animal model of Autoimmune Myocarditis characterized by the appearance of multinucleated giant cells. EAM was induced by injecting Lewis rats subcutaneously in the footpads with 1.0 mg of human cardiac myosin in an equal volume of Freund's complete adjuvant (FCA) on days 0 and 7. In experiment 1, we evaluated the effect of long-term anti-alpha beta TCR antibody therapy on prevention of progression of EAM. Long-term administration of anti-alpha beta TCR antibody prevented progression of EAM in a dose-dependent manner. Flow cytometry performed at the time of sacrifice showed that the percentage of alpha beta T cells in lymph nodes and spleen was similar in the control group and the group in which almost no histologic evidence of Myocarditis was found. In experiment 2, we examined the effects of short-term therapy. Rats were killed at different stages and pathologic specimens were examined. Short-term therapy delayed the onset of Myocarditis. Results of flow cytometry suggested that impairment of antigen recognition or T cell function by occupancy of the TCR rather than depletion of TCR was the mechanism responsible for suppression of EAM.
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Cardioprotective effects of recombinant human erythropoietin in rats with Experimental Autoimmune Myocarditis.
Biochemical and biophysical research communications, 2006Co-Authors: Wataru Mitsuma, Koichi Fuse, Haruo Hanawa, Makoto Kodama, Masahiro Ito, Kiminori Kato, Kazuki Okamura, Shiro Minagawa, Ken Toba, Mikio NakazawaAbstract:Erythropoietin (EPO) has been known to have cytoprotective effects on several types of tissues, presumably through modulation of apoptosis and inflammation. The effect of EPO on myocardial inflammation, however, has not yet been clarified. We investigated the cardioprotective effects of EPO in rats with Experimental Autoimmune Myocarditis (EAM). Seven-week-old Lewis rats immunized with cardiac myosin were treated either with EPO or vehicle and were examined on day 22. EPO attenuated the functional and histological severity of EAM along with suppression of mRNAs of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the hearts as well as a reduction of apoptotic cardiomyocytes. The EPO receptor (EPO-R) was upregulated in the myocardium of EAM compared with that of healthy rats. These results may suggest that EPO ameliorated the progression of EAM by modulating myocardial inflammation and apoptosis.
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FR167653 suppresses the progression of Experimental Autoimmune Myocarditis.
Molecular and cellular biochemistry, 2003Co-Authors: Seitaro Maruyama, Koichi Fuse, Haruo Hanawa, Makoto Kodama, Satoru Hirono, Yuji Okura, Kiminori Kato, Mikio Nakazawa, Osamu Nakagawa, Takashi MiidaAbstract:Experimental Autoimmune Myocarditis (EAM) induced in rats by injection of cardiac myosin is an animal model of human Myocarditis and post-Myocarditis dilated cardiomyopathy. It has been reported that proinflammatory cytokines play crucial roles in the induction of EAM and in the progression of myocardial injury in this disease. FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8-(4-pyridyl) pyrazolo [5,1-c] [1,2,4] triazin-2-yl]-2-phenylethanedione sulfate monohydrate) as been reported to suppress tumor necrosis factor-alpha (TNF-alpha). We hypothesized that FR167653 would suppress the progression of EAM if TNF-alpha and/or interleukin-1 beta (IL-1beta) were the culprit cytokines in EAM. To investigate the effects of FR167653 in EAM, FR167653 was given to rats for 4 weeks, immediately after they had been immunized with cardiac myosin. The ratio of heart weight to body weight and the area of inflammatory lesions were less in the FR167653 groups than in the control rats. FR167653 reduced serum sialic acid levels significantly. The control group showed a deterioration in cardiac function. The FR167653 groups had significantly better hemodynamic parameters, including improved left ventricular end-diastolic pressure, central venous pressure, aortic pressure, and positive and negative left ventricular pressure derivatives. mRNA expression of IL-1beta in the heart was significantly lower in rats given FR167653. However, mRNA of TNF-alpha was not detected in any groups. Our results suggest that FR167653 suppresses the development of Myocarditis by suppression of IL-1beta.
