Combined effects of aging and inflammation on renin-angiotensin system mediate mitochondrial dysfunction and phenotypic changes in cardiomyopathies

Tyesha N. Burks, Ruth Marx, Laura Powell, Jasma Rucker, Djahida Bedja, Elisa Heacock, Barbara J. Smith, D. Brian Foster, David Kass, Brian O'Rourke, Jeremy D. Walston, Peter M. Abadir*

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Citations (Scopus)
3 Downloads (Pure)

Abstract

Although the effects of aging and inflammation on the health of the cardiac muscle are well documented, the combined effects of aging and chronic inflammation on cardiac muscle are largely unknown. The renin-angiotensin system (RAS) has been linked independently to both aging and inflammation, but is understudied in the context of their collective effect. Thus, we investigated localized cardiac angiotensin II type I and type II receptors (AT1R, AT2R), downstream effectors, and phenotypic outcomes using mouse models of the combination of aging and inflammation and compared it to a model of aging and a model of inflammation. We show molecular distinction in the combined effect of aging and inflammation as compared to each independently. The combination maintained an increased AT1R:AT2R and expression of Nox2 and exhibited the lowest activity of antioxidants. Despite signaling pathway differences, the combined effect shared phenotypic similarities with aging including oxidative damage, fibrosis, and hypertrophy. These phenotypic similarities have dubbed inflammatory conditions as premature aging, but they are, in fact, molecularly distinct. Moreover, treatment with an AT1R blocker, losartan, selectively reversed the signaling changes and ameliorated adverse phenotypic effects in the combination of aging and inflammation as well as each independently.

Original languageEnglish
Pages (from-to)11979-11993
Number of pages15
JournalOncotarget
Volume6
Issue number14
DOIs
Publication statusPublished - 20 May 2015
Externally publishedYes

Bibliographical note

Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Aging
  • AT1R
  • Heart
  • Inflammation
  • Mitochondria

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