Experimental autoimmune myocarditis of rats induced by immunization with cardiac myosin: In vivo evidence of cell-mediated myocardial injury M. Kodama, T. Izumi, A. Shibata. First Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan

1990 ◽  
Vol 22 ◽  
pp. S24 ◽  
Keyword(s):  
Internal Medicine ◽  
Myocardial Injury ◽  
Cardiac Myosin ◽  
Autoimmune Myocarditis ◽  
School Of Medicine ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune

scholarly journals Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats

2012 ◽  
Vol 303 (9) ◽  
pp. H1114-H1127 ◽  
Author(s):  
Pablo Nakagawa ◽  
Yunhe Liu ◽  
Tang-Dong Liao ◽  
Xiaojuan Chen ◽  
Germán E. González ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Adhesion Molecules ◽  
Cardiac Dysfunction ◽  
Myocardial Injury ◽  
Cardiac Myosin ◽  
Autoimmune Myocarditis ◽  
Cell Responses ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune

Myocarditis is commonly associated with cardiotropic infections and has been linked to development of autoimmunity. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring tetrapeptide that prevents inflammation and fibrosis in hypertension and other cardiovascular diseases; however, its effect on autoimmune-mediated cardiac diseases remains unknown. We studied the effects of Ac-SDKP in experimental autoimmune myocarditis (EAM), a model of T cell-mediated autoimmune disease. This study was conducted to test the hypothesis that Ac-SDKP prevents autoimmune myocardial injury by modulating the immune responses. Lewis rats were immunized with porcine cardiac myosin and treated with Ac-SDKP or vehicle. In EAM, Ac-SDKP prevented both systolic and diastolic cardiac dysfunction, remodeling as shown by hypertrophy and fibrosis, and cell-mediated immune responses without affecting myosin-specific autoantibodies or antigen-specific T cell responses. In addition, Ac-SDKP reduced cardiac infiltration by macrophages, dendritic cells, and T cells, pro-inflammatory cytokines [interleukin (IL)-1α, tumor necrosis factor-α, IL-2, IL-17] and chemokines (cytokine-induced neutrophil chemoattractant-1, interferon-γ-induced protein 10), cell adhesion molecules (intercellular adhesion molecule-1, L-selectin), and matrix metalloproteinases (MMP). Ac-SDKP prevents autoimmune cardiac dysfunction and remodeling without reducing the production of autoantibodies or T cell responses to cardiac myosin. The protective effects of Ac-SDKP in autoimmune myocardial injury are most likely mediated by inhibition of 1) innate and adaptive immune cell infiltration and 2) expression of proinflammatory mediators such as cytokines, chemokines, adhesion molecules, and MMPs.

scholarly journals RIP1/RIP3/MLKL Mediates Myocardial Function Through Necroptosis in Experimental Autoimmune Myocarditis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yujing Wu ◽  
Zhenzhong Zheng ◽  
Xiantong Cao ◽  
Qing Yang ◽  
Vikram Norton ◽  
...  
Keyword(s):  
Cell Death ◽  
Myocardial Function ◽  
Viral Myocarditis ◽  
Cardiac Myosin ◽  
Autoimmune Myocarditis ◽  
Potential Therapeutic Target ◽  
Inflammatory Infiltration ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune

Cardiomyopathy often leads to dilated cardiomyopathy (DCM) when caused by viral myocarditis. Apoptosis is long considered as the principal process of cell death in cardiomyocytes, but programmed necrosis or necroptosis is recently believed to play an important role in cardiomyocyte cell death. We investigated the role of necroptosis and its interdependency with other processes of cell death, autophagy, and apoptosis in a rat system of experimental autoimmune myocarditis (EAM). We successfully created a rat model system of EAM by injecting porcine cardiac myosin (PCM) and showed that in EAM, all three forms of cell death increase considerably, resulting in the deterioration of cardiac conditions with an increase in inflammatory infiltration in cardiomyocytes. To explore whether necroptosis occurs in EAM rats independent of autophagy, we treated EAM rats with a RIP1/RIP3/MLKL kinase-mediated necroptosis inhibitor, Necrostatin-1 (Nec-1). In Nec-1 treated rats, cell death proceeds through apoptosis but has no significant effect on autophagy. In contrast, autophagy inhibitor 3-Methyl Adenine (3-MA) increases necroptosis, implying that blockage of autophagy must be compensated through necroptosis. Caspase 8 inhibitor zVAD-fmk blocks apoptosis but increases both necroptosis and autophagy. However, all necroptosis, apoptosis, and autophagy inhibitors independently reduce inflammatory infiltration in cardiomyocytes and improve cardiac conditions. Since apoptosis or autophagy is involved in many important cellular aspects, instead of suppressing these two major cell death processes, Nec1 can be developed as a potential therapeutic target for inflammatory myocarditis.

Time course of gene expression in rat experimental autoimmune myocarditis

2002 ◽  
Vol 103 (6) ◽  
pp. 623-632 ◽  
Author(s):  
Haruo HANAWA ◽  
Satoru ABE ◽  
Manabu HAYASHI ◽  
Tsuyoshi YOSHIDA ◽  
Kaori YOSHIDA ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Time Course ◽  
Collagen Type ◽  
Fold Increase ◽  
Cardiac Myosin ◽  
Autoimmune Myocarditis ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune

Genetic responses that characterize experimental autoimmune myocarditis (EAM) have not yet been determined. To investigate gene expression in the myocardium of EAM, absolute copy numbers of 44 mRNA species [calcium-handling proteins, contractile proteins, natriuretic peptides (NPs), cytokines, chemokines, growth factors, renin–angiotensin–aldosterone (RAA) system, endothelins (ETs) and extracellular matrix] in synthesized cDNA from a fixed quantity of total heart RNA were assessed using real-time reverse-transcriptase PCR at days 0, 14, 21 and 28 after immunization. α-Cardiac myosin showed a 26.3-fold decrease and β-cardiac myosin a 3.75-fold increase at day 14. Atrial NP and brain NP increased 47.7- and 6.35-fold at days 21 and 14 respectively. Angiotensin II type 1 receptor, angiotensin-converting enzyme and ET1 increased 22.3-fold at day 21, 6.30-fold at day 21 and 16.8-fold at day 14 respectively. Aldosterone receptor decreased 2.15-fold at day 14, but aldosterone synthetase was detected only at days 14 and 21. Interleukin (IL)-2, IL-10, interferon-γ and monocyte chemo-attractant protein-1 increased 9.08-fold at day 14, 398-fold at day 21, 43.1-fold at day 14 and 142-fold at day 14 respectively. Collagen type 3, collagen type 1 and fibronectin increased 34.6-, 1.74- and 44.4-fold respectively at day 21. Interestingly, osteopontin showed a 4540-fold increase and it was the highest mRNA of all at day 14. An isoform of cardiac myosin and NP are dramatically changed in EAM. RAA system and ET expressions are changed differently during the EAM time course. Cytokine, chemokine and extracellular matrix greatly increase and, in particular, large numbers of osteopontin mRNA are expressed in early EAM.

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