The adenosine A2A receptor - myocardial protectant and coronary target in endotoxemia

Reichelt, Melissa E., Ashton, Kevin J., Tan, Xing Lin, Mustafa, S. Jamal, Ledent, Catherine, Delbridge, Lea M. D., Hofmann, Polly A., Headrick, John P. and Morrison, R. Ray (2013) The adenosine A2A receptor - myocardial protectant and coronary target in endotoxemia. International Journal of Cardiology, 166 3: 672-680. doi:10.1016/j.ijcard.2011.11.075

Author Reichelt, Melissa E.
Ashton, Kevin J.
Tan, Xing Lin
Mustafa, S. Jamal
Ledent, Catherine
Delbridge, Lea M. D.
Hofmann, Polly A.
Headrick, John P.
Morrison, R. Ray
Title The adenosine A2A receptor - myocardial protectant and coronary target in endotoxemia
Formatted title
The adenosine A2A receptor - myocardial protectant and coronary target in endotoxemia
Journal name International Journal of Cardiology   Check publisher's open access policy
ISSN 1874-1754
Publication date 2013-07-01
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.ijcard.2011.11.075
Open Access Status Not yet assessed
Volume 166
Issue 3
Start page 672
End page 680
Total pages 9
Place of publication E Park, Shannon, Clare Ireland
Publisher Elsevier Ireland
Language eng
Formatted abstract
Background: Cardiac injury and dysfunction are contributors to disease progression and mortality in sepsis. This study evaluated the cardiovascular role of intrinsic A2A adenosine receptor (A2AAR) activity during lipopolysaccharide (LPS)-induced inflammation.

Methods: We assessed the impact of 24 h of LPS challenge (20 mg/kg, IP) on cardiac injury, coronary function and inflammatory mediator levels in Wild-Type (WT) mice and mice lacking functional A2AARs (A2AAR KO).

Results: Cardiac injury was evident in LPS-treated WTs, with ∼7-fold elevation in serum cardiac troponin I (cTnI), and significant ventricular and coronary dysfunction. Absence of A2AARs increased LPS-provoked cTnI release at 24 h by 3-fold without additional demise of contraction function. Importantly, A2AAR deletion per se emulated detrimental effects of LPS on coronary function, and LPS was without effect in coronary vessels lacking A2AARs. Effects of A2AAR KO were independent of major shifts in circulating C-reactive protein (CRP) and haptoglobin. Cytokine responses were largely insensitive to A2AAR deletion; substantial LPS-induced elevations (up to 100-fold) in IFN-γ and IL-10 were unaltered in A2AAR KO mice, as were levels of IL-4 and TNF-α. However, late elevations in IL-2 and IL-5 were differentially modulated by A2AAR KO (IL-2 reduced, IL-5 increased). Data demonstrate that in the context of LPS-triggered cardiac and coronary injury, A2AAR activity protects myocardial viability without modifying contractile dysfunction, and selectively modulates cytokine (IL-2, IL-5) release. A2AARs also appear to be targeted by LPS in the coronary vasculature.

Conclusions: These experimental data suggest that preservation of A2AAR functionality might provide therapeutic benefit in human sepsis.
Keyword Adenosine receptors
Cardiac dysfunction
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
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