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

Autores
Nakagawa, Pablo; Liu, Yunhe; Liao, Tang Dong; Chen, Xiaojuan; González, Germán Esteban; Bobbitt, Kevin R.; Smolarek, Derek; Peterson, Ed L.; Kedl, Ross; Yang, Xiao Ping; Rhaleb, Nour Eddine; Carretero, Oscar A.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Nakagawa, Pablo. Henry Ford Hospital; Estados Unidos
Fil: Liu, Yunhe. Henry Ford Hospital; Estados Unidos
Fil: Liao, Tang Dong. Henry Ford Hospital; Estados Unidos
Fil: Chen, Xiaojuan. Henry Ford Hospital; Estados Unidos
Fil: González, Germán Esteban. Henry Ford Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bobbitt, Kevin R.. Henry Ford Hospital; Estados Unidos
Fil: Smolarek, Derek. Henry Ford Hospital; Estados Unidos
Fil: Peterson, Ed L.. Henry Ford Hospital; Estados Unidos
Fil: Kedl, Ross. University of Colorado; Estados Unidos
Fil: Yang, Xiao Ping. Henry Ford Hospital; Estados Unidos
Fil: Rhaleb, Nour Eddine. Henry Ford Hospital; Estados Unidos
Fil: Carretero, Oscar A.. Henry Ford Hospital; Estados Unidos
Materia
Cardiac Dysfunction
Cardiac Hypertrophy
Cd4+T Helper Lymphocytes
Delayed-Type Hypersensitivity
Experimental Autoimmune Myocarditis
N-Acetyl-Seryl-Aspartyl-Lysyl-Proline
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/67311
Acceder
id CONICETDig_ac96fba5fb20e13768490846182d1328
oai_identifier_str oai:ri.conicet.gov.ar:11336/67311
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in ratsNakagawa, PabloLiu, YunheLiao, Tang DongChen, XiaojuanGonzález, Germán EstebanBobbitt, Kevin R.Smolarek, DerekPeterson, Ed L.Kedl, RossYang, Xiao PingRhaleb, Nour EddineCarretero, Oscar A.Cardiac DysfunctionCardiac HypertrophyCd4+T Helper LymphocytesDelayed-Type HypersensitivityExperimental Autoimmune MyocarditisN-Acetyl-Seryl-Aspartyl-Lysyl-Prolinehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Myocarditis 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.Fil: Nakagawa, Pablo. Henry Ford Hospital; Estados UnidosFil: Liu, Yunhe. Henry Ford Hospital; Estados UnidosFil: Liao, Tang Dong. Henry Ford Hospital; Estados UnidosFil: Chen, Xiaojuan. Henry Ford Hospital; Estados UnidosFil: González, Germán Esteban. Henry Ford Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bobbitt, Kevin R.. Henry Ford Hospital; Estados UnidosFil: Smolarek, Derek. Henry Ford Hospital; Estados UnidosFil: Peterson, Ed L.. Henry Ford Hospital; Estados UnidosFil: Kedl, Ross. University of Colorado; Estados UnidosFil: Yang, Xiao Ping. Henry Ford Hospital; Estados UnidosFil: Rhaleb, Nour Eddine. Henry Ford Hospital; Estados UnidosFil: Carretero, Oscar A.. Henry Ford Hospital; Estados UnidosAmerican Physiological Society2012-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67311Nakagawa, Pablo; Liu, Yunhe; Liao, Tang Dong; Chen, Xiaojuan; González, Germán Esteban; et al.; Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats; American Physiological Society; American Journal of Physiology - Heart and Circulatory Physiology; 303; 9; 11-2012; 1-140363-6135CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajpheart.00300.2011info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/ajpheart.00300.2011info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:49:29Zoai:ri.conicet.gov.ar:11336/67311instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:49:29.673CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats
title Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats
spellingShingle Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats
Nakagawa, Pablo
Cardiac Dysfunction
Cardiac Hypertrophy
Cd4+T Helper Lymphocytes
Delayed-Type Hypersensitivity
Experimental Autoimmune Myocarditis
N-Acetyl-Seryl-Aspartyl-Lysyl-Proline
title_short Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats
title_full Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats
title_fullStr Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats
title_full_unstemmed Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats
title_sort Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats
dc.creator.none.fl_str_mv Nakagawa, Pablo
Liu, Yunhe
Liao, Tang Dong
Chen, Xiaojuan
González, Germán Esteban
Bobbitt, Kevin R.
Smolarek, Derek
Peterson, Ed L.
Kedl, Ross
Yang, Xiao Ping
Rhaleb, Nour Eddine
Carretero, Oscar A.
author Nakagawa, Pablo
author_facet Nakagawa, Pablo
Liu, Yunhe
Liao, Tang Dong
Chen, Xiaojuan
González, Germán Esteban
Bobbitt, Kevin R.
Smolarek, Derek
Peterson, Ed L.
Kedl, Ross
Yang, Xiao Ping
Rhaleb, Nour Eddine
Carretero, Oscar A.
author_role author
author2 Liu, Yunhe
Liao, Tang Dong
Chen, Xiaojuan
González, Germán Esteban
Bobbitt, Kevin R.
Smolarek, Derek
Peterson, Ed L.
Kedl, Ross
Yang, Xiao Ping
Rhaleb, Nour Eddine
Carretero, Oscar A.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cardiac Dysfunction
Cardiac Hypertrophy
Cd4+T Helper Lymphocytes
Delayed-Type Hypersensitivity
Experimental Autoimmune Myocarditis
N-Acetyl-Seryl-Aspartyl-Lysyl-Proline
topic Cardiac Dysfunction
Cardiac Hypertrophy
Cd4+T Helper Lymphocytes
Delayed-Type Hypersensitivity
Experimental Autoimmune Myocarditis
N-Acetyl-Seryl-Aspartyl-Lysyl-Proline
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Nakagawa, Pablo. Henry Ford Hospital; Estados Unidos
Fil: Liu, Yunhe. Henry Ford Hospital; Estados Unidos
Fil: Liao, Tang Dong. Henry Ford Hospital; Estados Unidos
Fil: Chen, Xiaojuan. Henry Ford Hospital; Estados Unidos
Fil: González, Germán Esteban. Henry Ford Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bobbitt, Kevin R.. Henry Ford Hospital; Estados Unidos
Fil: Smolarek, Derek. Henry Ford Hospital; Estados Unidos
Fil: Peterson, Ed L.. Henry Ford Hospital; Estados Unidos
Fil: Kedl, Ross. University of Colorado; Estados Unidos
Fil: Yang, Xiao Ping. Henry Ford Hospital; Estados Unidos
Fil: Rhaleb, Nour Eddine. Henry Ford Hospital; Estados Unidos
Fil: Carretero, Oscar A.. Henry Ford Hospital; Estados Unidos
description 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.
publishDate 2012
dc.date.none.fl_str_mv 2012-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/67311
Nakagawa, Pablo; Liu, Yunhe; Liao, Tang Dong; Chen, Xiaojuan; González, Germán Esteban; et al.; Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats; American Physiological Society; American Journal of Physiology - Heart and Circulatory Physiology; 303; 9; 11-2012; 1-14
0363-6135
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67311
identifier_str_mv Nakagawa, Pablo; Liu, Yunhe; Liao, Tang Dong; Chen, Xiaojuan; González, Germán Esteban; et al.; Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats; American Physiological Society; American Journal of Physiology - Heart and Circulatory Physiology; 303; 9; 11-2012; 1-14
0363-6135
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpheart.00300.2011
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/ajpheart.00300.2011
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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