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Myocardial aging as a T-cell–mediated phenomenon
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Advisor(s)
Abstract(s)
In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether immunological activity would influence myocardial structure and function in elderly mice. Morphological, functional, and molecular analyses revealed that the age-related myocardial impairment occurs in parallel with shifts in the composition of tissue-resident leukocytes and with an accumulation of activated CD4+Foxp3-(forkhead box P3) IFN-γ+T cells in the heart-draining lymph nodes. A comprehensive characterization of different aged immune-deficient mouse strains revealed that T cells significantly contribute to age-related myocardial inflammation and functional decline. Upon adoptive cell transfer, the T cells isolated from the mediastinal lymph node (med-LN) of aged animals exhibited increased cardiotropism, compared with cells purified from young donors or from other irrelevant sites. Nevertheless, these cells caused rather mild effects on cardiac functionality, indicating that myocardial aging might stem from a combination of intrinsic and extrinsic (immunological) factors. Taken together, the data herein presented indicate that heart-directed immune responses may spontaneously arise in the elderly, even in the absence of a clear tissue damage or concomitant infection. These observations might shed new light on the emerging role of T cells in myocardial diseases, which primarily affect the elderly population.
Description
This deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373357/
This publication hasn't any creative commons license associated.
This publication hasn't any creative commons license associated.
Keywords
myocardial aging T cells inflammation inflammaging
Citation
Myocardial aging as a T-cell–mediated phenomenon - Gustavo Campos Ramos, Anne van den Berg, Vânia Nunes-Silva, Johannes Weirather, Laura Peters, Matthias Burkard, Mike Friedrich, Jürgen Pinnecker, Marco Abeßer, Katrin G. Heinze, Kai Schuh, Niklas Beyersdorf, Thomas Kerkau, Jocelyne Demengeot, Stefan Frantz, Ulrich Hofmann Proceedings of the National Academy of Sciences Mar 2017, 114 (12) E2420-E2429; DOI: 10.1073/pnas.1621047114
Publisher
National Academy of Sciences