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Article
Selective effects of intrinsic A2AAR activity on cardiac and coronary injuries with LPS challenge
Heart, Lung and Circulation
  • Melissa E Reichelt, University of Melbourne
  • Kevin Ashton, Bond University
  • S Jamal Mustafa, St. Jude Children's Research Hospital, Memphis
  • B Tang, St. Jude Children's Research Hospital, Memphis
  • Catherine Ledent, University Libre de Bruxelles
  • Xing Lin Tan, St. Jude Childrens's Research Hospital, Memphis
  • John Patrick Headrick, University of Melbourne
  • R Ray Morrison, St. Jude Childrens's Research Hospital, Memphis
Date of this Version
7-23-2010
Document Type
Journal Article
Publication Details

Citation only

Reichelt, M., Ashton, K., Mustafa, S., Tang, B., Ledent, C., Tan, X., Headrick, J., Morrison R. (2010). Selective effects of intrinsic A2AAR activity on cardiac and coronary injuries with LPS challenge. Heart, Lung and Circulation, 19, S47.

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© Copyright Elsevier Ltd, 2010

Abstract

We assessed the impact of A2A adenosine receptor (A2AAR) knockout (KO) on LPS-triggered cardiovascular injuries, inflammation, gene expression and mortality. LPS precipitated cardiac injury, with 7-fold elevations in serum cardiac troponin I (cTnI) and 25–35% reductions in ventricular contractility. Coronary dysfunction was evident as a 20% reduction in reactive hyperaemic flows. A2AAR KO augmented cTnI release 3-fold without modifying ventricular dysfunction. Coronary effects of LPS and A2AAR KO were identical, and LPS no longer modified hyperaemia in A2AAR KO hearts. Effects of A2AAR activity were largely independent of shifts in acute phase reactants (CRP, haptoglobin) and circulating cytokines. Thus, up to 100-fold elevations in IFN-© and IL-10 with LPS were unaltered by A2AAR KO, as were changes in IL-4 and TNF-〈. Similarly, many of the ∼8000 LPS-responsive cardiac transcripts may contribute to injury (eg. 15-fold repression of protective adiponectin, 40-fold induction of Ca2+ binding proteins S100A8 and S100A9), yet were also insensitive to A2AAR KO. Mortality with LPS ± A2AAR KO was age- and sex-dependent, with no deaths in young (2–4 mth), 20% mortality in old (10–11 mth), and 4-fold enhanced mortality with A2AAR KO in old males only. Our data indicate that intrinsic A2AAR activity selectively augments survival in older males and limits cardiac damage (but not dysfunction) with LPS challenge. The A2AAR underlies LPS-dependent reductions in coronary reactivity. These subtle effects of A2AAR KO support selective but modest receptor engagement by endogenous ligands during LPS challenge, consistent with abilities of exogenous agonists to modify these processes.

Citation Information
Melissa E Reichelt, Kevin Ashton, S Jamal Mustafa, B Tang, et al.. "Selective effects of intrinsic A2AAR activity on cardiac and coronary injuries with LPS challenge" Heart, Lung and Circulation Vol. 19 (2010) p. S47 ISSN: 1444-2892
Available at: http://works.bepress.com/kevin_ashton/9/