Change of cardiac function in experimental autoimmune myocarditis is correlated with the expression of annexin VI

2009 ◽  
Vol 64 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Z. Bian ◽  
Q. Tang ◽  
H. Wu ◽  
J. Huang ◽  
D. Shen
Keyword(s):  
Cardiac Function ◽  
Autoimmune Myocarditis ◽  
Annexin Vi ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune

scholarly journals STAT4 silencing underlies a novel inhibitory role of microRNA-141-3p in inflammation response of mice with experimental autoimmune myocarditis

2019 ◽  
Vol 317 (3) ◽  
pp. H531-H540 ◽  
Author(s):  
Aiqun Pan ◽  
Yuying Tan ◽  
Zhihao Wang ◽  
Guoliang Xu
Keyword(s):  
Body Weight ◽  
Cardiac Function ◽  
Weight Ratio ◽  
Heart Weight ◽  
Inflammatory Factor ◽  
Body Weight Ratio ◽  
Autoimmune Myocarditis ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune

As an inflammatory disease afflicting the heart muscle, autoimmune myocarditis (AM) represents one of the foremost causes of heart failure. Accumulating evidence has implicated microRNAs (miRNAs) in the process of inflammation and autoimmunity. Hence, the current study aimed to investigate the mechanism by which miR-141-3p influences experimental AM (EAM). An EAM mouse model was established using 6-wk old male BALB/c mice, after which the expression of miR-141-3p and STAT4 was measured. Gain-of-function and loss-of-function investigations were performed to identify the functional role of miR-141-3p and STAT4 in EAM. Heart weight-to-body weight ratio, cardiac function, and degree of inflammation, as well as the levels of inflammation factors (IFN-γ, TNF-α, IL-2, IL-6, and IL-17) in the serum were detected. STAT4 was subsequently verified to be upregulated, and miR-141-3p was downregulated in the EAM mice. Furthermore, the overexpression of miR-141-3p or silencing of STAT4 was observed to reduce the heart weight-to-body weight ratio of EAM mice and improve cardiac function, while alleviating the degree of inflammatory cell infiltration in the myocardial tissue. Meanwhile, the overexpression of miR-141-3p was identified to diminish serum inflammatory factor levels by downregulating STAT4. Additionally, miR-141-3p could bind to STAT4 to downregulate its expression, ultimately mitigating inflammation and inducing an anti-inflammatory effect in EAM mice. Taken together, upregulation of miR-141-3p alleviates the inflammatory response in EAM mice by inhibiting STAT4, providing a promising intervention target for the molecular treatment of AM. NEW & NOTEWORTHY miR-141-3p is poorly expressed, and STAT4 is upregulated in experimental autoimmune myocarditis (EAM) mice. Overexpressing miR-141-3p inhibits EAM. miR-141-3p binds to and suppresses STAT4 expression. miR-141-3p overexpression inhibits inflammatory factors by downregulating STAT4. This study provides new insights into the treatment of autoimmune myocarditis.

Abstract 5261: Platelet-Depletion Ameliorates Cardiac Function and Disease Severity in Experimental Autoimmune Myocarditis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Martin Russ ◽  
Barbara Seliger ◽  
Steffen Hauptmann ◽  
Rene Marty ◽  
Jürgen Bukur ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Inflammatory Cardiomyopathy ◽  
Autoimmune Myocarditis ◽  
Severity Scores ◽  
Experimental Autoimmune Myocarditis ◽  
Platelet Depletion ◽  
Experimental Autoimmune

Introduction: Experimental Autoimmune Myocarditis (EAM) is a CD4+ T cell mediated model of inflammatory cardiomyopathy. Activated platelets express CD154, a molecule critical to adaptive immune responses, which has been implicated in platelet-mediated modulation of inflammation. Hypothesis: Platelets are critical for the generation of heart-specific, autoreactive T-cell responses in a model of experimental Autoimmune Myocarditis. Methods: BALB/c mice were immunized twice at day 0 and day 7 with 100μg alpha-MyHC-peptide (614–29) together with Complete Freund‘s adjuvant. Platelets were markedly depleted by i.v. injection of a GP1alpha antibody every 5th day (n=8). Control mice were injected with a non-depleting isotype antibody (n=8). Mice were assessed at day 28 for heart dimensions and cardiac function using echocardiography. After lethal anesthesia, hearts were removed and analyzed for heart weight/body weight ratio and histological severity scores. CD4+ T-cells were isolated from spleens, and analyzed for CD154 and IL-17 expression using FACS after in vitro re-stimulation on alpha-MyHC pulsed, irradiated antigen presenting cells. Results: Modest platelet depletion protected from left ventricular dilatation, and preserved left ventricular ejection fraction in immunized mice. Myocarditis prevalence and severity scores were significantly reduced in depleted animals. Relative numbers of spleen-derived CD4+ T-cells expressing CD154 or IL-17, were significantly reduced in the treatment group (table ). Conclusion: Our findings suggest that platelets might play a critical role in the development of heart-specific autoimmunity and cardiomyopathy. Further studies are needed to confirm these findings, which suggest a novel treatment approach for inflammatory cardiomyopathy. Echocardiography - Histology - FACS

scholarly journals Transplantation of Fibroblast Sheets with Blood Mononuclear Cell Culture Exerts Cardioprotective Effects by Enhancing Anti-Inflammation and Vasculogenic Potential in Rat Experimental Autoimmune Myocarditis Model

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 106
Author(s):  
Kaori Sekine ◽  
Akira T. Kawaguchi ◽  
Masaki Miyazawa ◽  
Haruo Hanawa ◽  
Shinichi Matsuda ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Mononuclear Cells ◽  
Therapeutic Option ◽  
Cell Sheet ◽  
Left Ventricular ◽  
Fulminant Myocarditis ◽  
Autoimmune Myocarditis ◽  
Experimental Autoimmune Myocarditis ◽  
Anti Inflammatory ◽  
Experimental Autoimmune

Fulminant myocarditis causes impaired cardiac function, leading to poor prognosis and heart failure. Cell sheet engineering is an effective therapeutic option for improving cardiac function. Naïve blood mononuclear cells (MNCs) have been previously shown to enhance the quality and quantity of cellular fractions (QQMNCs) with anti-inflammatory and vasculogenic potential using the one culture system. Herein, we investigated whether autologous cell sheet transplant with QQMNCs improves cardiac function in a rat model with experimental autoimmune myocarditis (EAM). Fibroblast sheets (F-sheet), prepared from EAM rats, were co-cultured with or without QQMNCs (QQ+F sheet) on temperature-responsive dishes. QQ+F sheet induced higher expression of anti-inflammatory and vasculogenic genes (Vegf-b, Hgf, Il-10, and Mrc1/Cd206) than the F sheet. EAM rats were transplanted with either QQ+F sheet or F-sheet, and the left ventricular (LV) hemodynamic analysis was performed using cardiac catheterization. Among the three groups (QQ+F sheet, F-sheet, operation control), the QQ+F sheet transplant group showed alleviation of end-diastolic pressure–volume relationship on a volume load to the same level as that in the healthy group. Histological analysis revealed that QQ+F sheet transplantation promoted revascularization and mitigated fibrosis by limiting LV remodeling. Therefore, autologous QQMNC-modified F-sheets may be a beneficial therapeutic option for EAM.

scholarly journals Sex-Specific Differences of the Inflammatory State in Experimental Autoimmune Myocarditis

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Luisa Barcena ◽  
Sarah Jeuthe ◽  
Maximilian H. Niehues ◽  
Sofya Pozdniakova ◽  
Natalie Haritonow ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Female Rats ◽  
Male Rats ◽  
Inflammatory Factors ◽  
Autoimmune Myocarditis ◽  
Male And Female Rats ◽  
Inflammatory Phenotype ◽  
Experimental Autoimmune Myocarditis ◽  
Anti Inflammatory ◽  
Experimental Autoimmune

Increasing evidence suggests male sex as a potential risk factor for a higher incidence of cardiac fibrosis, stronger cardiac inflammation, and dilated cardiomyopathy (DCM) in human myocarditis. Chronic activation of the immune response in myocarditis may trigger autoimmunity. The experimental autoimmune myocarditis (EAM) model has been well established for the study of autoimmune myocarditis, however the role of sex in this pathology has not been fully explored. In this study, we investigated sex differences in the inflammatory response in the EAM model. We analyzed the cardiac function, as well as the inflammatory stage and fibrosis formation in the heart of EAM male and female rats. 21 days after induction of EAM, male EAM rats showed a decreased ejection fraction, stroke volume and cardiac output, while females did not. A significantly elevated number of infiltrates was detected in myocardium in both sexes, indicating the activation of macrophages following EAM induction. The level of anti-inflammatory macrophages (CD68+ ArgI+) was only significantly increased in female hearts. The expression of Col3A1 and fibrosis formation were more prominent in males. Furthermore, prominent pro-inflammatory factors were increased only in male rats. These findings indicate sex-specific alterations in the inflammatory stage of EAM, with a pro-inflammatory phenotype appearing in males and an anti-inflammatory phenotype in females, which both significantly affect cardiac function in autoimmune myocarditis.

scholarly journals Programmed Death-Ligand 2 Deficiency Exacerbates Experimental Autoimmune Myocarditis in Mice

2021 ◽  
Vol 22 (3) ◽  
pp. 1426
Author(s):  
Siqi Li ◽  
Kazuko Tajiri ◽  
Nobuyuki Murakoshi ◽  
DongZhu Xu ◽  
Saori Yonebayashi ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Receptor ◽  
Cd4 T Cell ◽  
Myocardial Inflammation ◽  
Autoimmune Myocarditis ◽  
Inflammatory Infiltration ◽  
Programmed Death ◽  
Experimental Autoimmune Myocarditis ◽  
Deficient Mice ◽  
Experimental Autoimmune

Programmed death ligand 2 (PD-L2) is the second ligand of programmed death 1 (PD-1) protein. In autoimmune myocarditis, the protective roles of PD-1 and its first ligand programmed death ligand 1 (PD-L1) have been well documented; however, the role of PD-L2 remains unknown. In this study, we report that PD-L2 deficiency exacerbates myocardial inflammation in mice with experimental autoimmune myocarditis (EAM). EAM was established in wild-type (WT) and PD-L2-deficient mice by immunization with murine cardiac myosin peptide. We found that PD-L2-deficient mice had more serious inflammatory infiltration in the heart and a significantly higher myocarditis severity score than WT mice. PD-L2-deficient dendritic cells (DCs) enhanced CD4+ T cell proliferation in the presence of T cell receptor and CD28 signaling. These data suggest that PD-L2 on DCs protects against autoreactive CD4+ T cell expansion and severe inflammation in mice with EAM.

Immunomodulatory Effects of Erythropoietin on the Experimental Autoimmune Myocarditis of Rats

2005 ◽  
Vol 11 (9) ◽  
pp. S284
Author(s):  
Hisahito Shinagawa ◽  
Takayuki Inomata ◽  
Hironari Nakano ◽  
Toshimi Koitabashi ◽  
Tsutomu Ohsaka ◽  
...  
Keyword(s):  
Immunomodulatory Effects ◽  
Autoimmune Myocarditis ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune
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