Characterization of Transverse Aortic Constriction in Mice Based on the Specific Recruitment of Leukocytes to the Hypertrophic Myocardium and the Aorta Ascendens

Transverse aortic constriction (TAC) is a model that mimics pressure overload-induced left ventricular (LV) hypertrophy in mice. Alterations in immune cell functionality can promote cardiac and vascular remodeling. In the present study, we characterized the time course in innate immune cell dynamics...

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Autores principales:	Jan Lukas Kleiner, Odilia Köpke, Anton Faron, Yunyang Zhang, Jan Cornelssen, Mark Coburn, Stilla Frede, Lars Eichhorn, Christina Katharina Weisheit
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Pathology RB1-214
Acceso en línea:	https://doaj.org/article/89db006aff744f329ea255d00fa9823f
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spelling	oai:doaj.org-article:89db006aff744f329ea255d00fa9823f2021-11-15T01:19:34ZCharacterization of Transverse Aortic Constriction in Mice Based on the Specific Recruitment of Leukocytes to the Hypertrophic Myocardium and the Aorta Ascendens1466-186110.1155/2021/1376859https://doaj.org/article/89db006aff744f329ea255d00fa9823f2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/1376859https://doaj.org/toc/1466-1861Transverse aortic constriction (TAC) is a model that mimics pressure overload-induced left ventricular (LV) hypertrophy in mice. Alterations in immune cell functionality can promote cardiac and vascular remodeling. In the present study, we characterized the time course in innate immune cell dynamics in response to TAC in the different tissues of mice. It was determined whether TAC induces a characteristic leukocyte-driven immune response in the myocardium, aorta ascendens and descendens, spleen, blood, and draining lymph nodes supported by cytokine-driven chemotaxis in mice at 3, 6, and 21 days following surgery. We used complex flow cytometry staining combinations to characterize the various innate immune cell subsets and a multiplex array to determine cytokine concentrations in the serum. The results of the current study indicated that leukocytes accumulate in the myocardium and aorta ascendens in response to TAC. The leukocyte dynamics in the myocardium were dominated by the Ly6Clow macrophages with an early accumulation, whereas the response in the aorta ascendens was characterized by a long-lasting proinflammatory phenotype driven by Ly6Chigh macrophages, neutrophils, and activated DCs. In contrast to the high-pressure environment of the aorta ascendens, the tissue of the aorta descendens did not react to TAC with any leukocyte increase. The levels of proinflammatory cytokines in the blood were elevated in response to TAC, indicating a systemic reaction. Moreover, our findings strongly suggest that cardiac macrophages could origin from splenic pools and reach the site of the inflammation via the blood. Based on the current findings, it can be concluded that the high-pressure conditions in the aorta ascendens cause a characteristic immune response, dominated by the accumulation of leukocytes and the activation of DCs that varies in comparison to the immune cell dynamics in the myocardium and the aorta descendens.Jan Lukas KleinerOdilia KöpkeAnton FaronYunyang ZhangJan CornelssenMark CoburnStilla FredeLars EichhornChristina Katharina WeisheitHindawi LimitedarticlePathologyRB1-214ENMediators of Inflammation, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pathology RB1-214
spellingShingle	Pathology RB1-214 Jan Lukas Kleiner Odilia Köpke Anton Faron Yunyang Zhang Jan Cornelssen Mark Coburn Stilla Frede Lars Eichhorn Christina Katharina Weisheit Characterization of Transverse Aortic Constriction in Mice Based on the Specific Recruitment of Leukocytes to the Hypertrophic Myocardium and the Aorta Ascendens
description	Transverse aortic constriction (TAC) is a model that mimics pressure overload-induced left ventricular (LV) hypertrophy in mice. Alterations in immune cell functionality can promote cardiac and vascular remodeling. In the present study, we characterized the time course in innate immune cell dynamics in response to TAC in the different tissues of mice. It was determined whether TAC induces a characteristic leukocyte-driven immune response in the myocardium, aorta ascendens and descendens, spleen, blood, and draining lymph nodes supported by cytokine-driven chemotaxis in mice at 3, 6, and 21 days following surgery. We used complex flow cytometry staining combinations to characterize the various innate immune cell subsets and a multiplex array to determine cytokine concentrations in the serum. The results of the current study indicated that leukocytes accumulate in the myocardium and aorta ascendens in response to TAC. The leukocyte dynamics in the myocardium were dominated by the Ly6Clow macrophages with an early accumulation, whereas the response in the aorta ascendens was characterized by a long-lasting proinflammatory phenotype driven by Ly6Chigh macrophages, neutrophils, and activated DCs. In contrast to the high-pressure environment of the aorta ascendens, the tissue of the aorta descendens did not react to TAC with any leukocyte increase. The levels of proinflammatory cytokines in the blood were elevated in response to TAC, indicating a systemic reaction. Moreover, our findings strongly suggest that cardiac macrophages could origin from splenic pools and reach the site of the inflammation via the blood. Based on the current findings, it can be concluded that the high-pressure conditions in the aorta ascendens cause a characteristic immune response, dominated by the accumulation of leukocytes and the activation of DCs that varies in comparison to the immune cell dynamics in the myocardium and the aorta descendens.
format	article
author	Jan Lukas Kleiner Odilia Köpke Anton Faron Yunyang Zhang Jan Cornelssen Mark Coburn Stilla Frede Lars Eichhorn Christina Katharina Weisheit
author_facet	Jan Lukas Kleiner Odilia Köpke Anton Faron Yunyang Zhang Jan Cornelssen Mark Coburn Stilla Frede Lars Eichhorn Christina Katharina Weisheit
author_sort	Jan Lukas Kleiner
title	Characterization of Transverse Aortic Constriction in Mice Based on the Specific Recruitment of Leukocytes to the Hypertrophic Myocardium and the Aorta Ascendens
title_short	Characterization of Transverse Aortic Constriction in Mice Based on the Specific Recruitment of Leukocytes to the Hypertrophic Myocardium and the Aorta Ascendens
title_full	Characterization of Transverse Aortic Constriction in Mice Based on the Specific Recruitment of Leukocytes to the Hypertrophic Myocardium and the Aorta Ascendens
title_fullStr	Characterization of Transverse Aortic Constriction in Mice Based on the Specific Recruitment of Leukocytes to the Hypertrophic Myocardium and the Aorta Ascendens
title_full_unstemmed	Characterization of Transverse Aortic Constriction in Mice Based on the Specific Recruitment of Leukocytes to the Hypertrophic Myocardium and the Aorta Ascendens
title_sort	characterization of transverse aortic constriction in mice based on the specific recruitment of leukocytes to the hypertrophic myocardium and the aorta ascendens
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/89db006aff744f329ea255d00fa9823f
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Characterization of Transverse Aortic Constriction in Mice Based on the Specific Recruitment of Leukocytes to the Hypertrophic Myocardium and the Aorta Ascendens

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