Characterization of the immune cell repertoire in myocardial infarction and heart failure

Myocardial infarction (MI) is the major cause of morbidity and mortality worldwide. The\nmost common cause of myocardial infarction is the partial or complete occlusion of\ncoronary arteries by the erosion or rupture of a vulnerable atherosclerotic plaque. MI\nis the prevailing cause of heart failur...

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Autor principal: Mitre, Lucia Sol
Otros Autores: Marchini, Timoteo
Formato: Tesis de maestría acceptedVersion
Lenguaje:Inglés
Publicado: Facultad de Farmacia y Bioquímica 2019
Materias:
Infarto de miocardio
Células inmunitarias
Insuficiencia cardíaca
Myocardial Infarction
Immune cell repertoire
Heart failure
Ciencias de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5928
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5928.dir/5928.PDF
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Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
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spelling I28-R145-HWA_59282022-04-12 Myocardial infarction (MI) is the major cause of morbidity and mortality worldwide. The\nmost common cause of myocardial infarction is the partial or complete occlusion of\ncoronary arteries by the erosion or rupture of a vulnerable atherosclerotic plaque. MI\nis the prevailing cause of heart failure, which develops due to post-infarction left\nventricular remodeling, and therefore a huge problem in medical practice. Current\ntherapies are limited to mechanical revascularization strategies that restore blood flow,\nbut do not specifically target post-MI cardiac remodeling. Cardiac healing and\nremodeling are orchestrated, improved or aggravated, by cells of the immune system\nthat infiltrate the heart following myocardial infarction. Thus, immune-modulatory or\ncell-targeting strategies have been proposed in the combat against adverse cardiac\nremodeling, but the temporal and spatial parameters of cardiac immune cells are only\npartially understood.\nIn this thesis, I present a comprehensive cellular screening strategy by state-of-the-art\n15-color flow cytometry to define leukocyte infiltration in the heart. While recent studies\nhave focused on specific immune cell subsets, this study allows -for the first time- to\ndirectly compare leukocyte subsets from various hematopoietic lineages. In large parts\nmy results identify B cells, CD4+ T cells, and DCs as predominant lymphocytes\ninfiltrating the injured heart, while macrophages represent the most frequent\nleukocytes in the healthy heart. These results argue for an adaptive immune response\ninvolving antigen-presenting DCs and effector T and B cells. Indeed, cytokine profiles\nfrom cardiac lymphocyte showed an increase of TNF?, IFN?, IL-17, granzyme and\nGMCSF and the antigen-regulated activation marker CD40L at the late time-point 21\ndays after MI, which is consistent with the build-up of a relevant immune memory.\nAmong all regulated cell types, I identified potential new candidates, including NK cells\nthat peaked early only in the injured myocardium and ?/? T cells that represented a\nsmall population that infiltrated older ischemic section of the heart. Various control\nconditions, including models of non-ischemic heart injury by pressure-overload and\nnon-sustained ischemic injury by surgical ischemia/reperfusion (I/R) as well as the\nquantification of systemic leukocytes subsets suggest specificity of these findings.\nMy findings may inspire the functional evaluation of candidate cell subsets and\ncytokines in direct follow-up studies. These results may be helpful to establish novel\ncellular targets for future MI therapy. Fil: Mitre, Lucia Sol. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Marchini, Timoteo Facultad de Farmacia y Bioquímica Zirlik, Andreas Mitre, Lucia Sol 2019-03-06 application/pdf Buchholz, Bruno Carrera Silva, Eugenio Hannibal, Luciana Infarto de miocardio Células inmunitarias Insuficiencia cardíaca Myocardial Infarction Immune cell repertoire Heart failure eng Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la vida Characterization of the immune cell repertoire in myocardial infarction and heart failure info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5928 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5928.dir/5928.PDF
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Inglés
orig_language_str_mv eng
topic Infarto de miocardio
Células inmunitarias
Insuficiencia cardíaca
Myocardial Infarction
Immune cell repertoire
Heart failure
Ciencias de la vida
spellingShingle Infarto de miocardio
Células inmunitarias
Insuficiencia cardíaca
Myocardial Infarction
Immune cell repertoire
Heart failure
Ciencias de la vida
Mitre, Lucia Sol
Characterization of the immune cell repertoire in myocardial infarction and heart failure
topic_facet Infarto de miocardio
Células inmunitarias
Insuficiencia cardíaca
Myocardial Infarction
Immune cell repertoire
Heart failure
Ciencias de la vida
description Myocardial infarction (MI) is the major cause of morbidity and mortality worldwide. The\nmost common cause of myocardial infarction is the partial or complete occlusion of\ncoronary arteries by the erosion or rupture of a vulnerable atherosclerotic plaque. MI\nis the prevailing cause of heart failure, which develops due to post-infarction left\nventricular remodeling, and therefore a huge problem in medical practice. Current\ntherapies are limited to mechanical revascularization strategies that restore blood flow,\nbut do not specifically target post-MI cardiac remodeling. Cardiac healing and\nremodeling are orchestrated, improved or aggravated, by cells of the immune system\nthat infiltrate the heart following myocardial infarction. Thus, immune-modulatory or\ncell-targeting strategies have been proposed in the combat against adverse cardiac\nremodeling, but the temporal and spatial parameters of cardiac immune cells are only\npartially understood.\nIn this thesis, I present a comprehensive cellular screening strategy by state-of-the-art\n15-color flow cytometry to define leukocyte infiltration in the heart. While recent studies\nhave focused on specific immune cell subsets, this study allows -for the first time- to\ndirectly compare leukocyte subsets from various hematopoietic lineages. In large parts\nmy results identify B cells, CD4+ T cells, and DCs as predominant lymphocytes\ninfiltrating the injured heart, while macrophages represent the most frequent\nleukocytes in the healthy heart. These results argue for an adaptive immune response\ninvolving antigen-presenting DCs and effector T and B cells. Indeed, cytokine profiles\nfrom cardiac lymphocyte showed an increase of TNF?, IFN?, IL-17, granzyme and\nGMCSF and the antigen-regulated activation marker CD40L at the late time-point 21\ndays after MI, which is consistent with the build-up of a relevant immune memory.\nAmong all regulated cell types, I identified potential new candidates, including NK cells\nthat peaked early only in the injured myocardium and ?/? T cells that represented a\nsmall population that infiltrated older ischemic section of the heart. Various control\nconditions, including models of non-ischemic heart injury by pressure-overload and\nnon-sustained ischemic injury by surgical ischemia/reperfusion (I/R) as well as the\nquantification of systemic leukocytes subsets suggest specificity of these findings.\nMy findings may inspire the functional evaluation of candidate cell subsets and\ncytokines in direct follow-up studies. These results may be helpful to establish novel\ncellular targets for future MI therapy.
author2 Marchini, Timoteo
author_facet Marchini, Timoteo
Mitre, Lucia Sol
format Tesis de maestría
Tesis de maestría
acceptedVersion
author Mitre, Lucia Sol
author_sort Mitre, Lucia Sol
title Characterization of the immune cell repertoire in myocardial infarction and heart failure
title_short Characterization of the immune cell repertoire in myocardial infarction and heart failure
title_full Characterization of the immune cell repertoire in myocardial infarction and heart failure
title_fullStr Characterization of the immune cell repertoire in myocardial infarction and heart failure
title_full_unstemmed Characterization of the immune cell repertoire in myocardial infarction and heart failure
title_sort characterization of the immune cell repertoire in myocardial infarction and heart failure
publisher Facultad de Farmacia y Bioquímica
publishDate 2019
url http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_5928
http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_5928.dir/5928.PDF
work_keys_str_mv AT mitreluciasol characterizationoftheimmunecellrepertoireinmyocardialinfarctionandheartfailure
_version_ 1766017554380226560

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