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

Melissa E. Reichelt*, Kevin J. Ashton, Xing Lin Tan, S. Jamal Mustafa, Catherine Ledent, Lea M D Delbridge, Polly A. Hofmann, John P. Headrick, R. Ray Morrison

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)


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, A 2AAR deletion per se emulated detrimental effects of LPS on coronary function, and LPS was without effect in coronary vessels lacking A 2AARs. 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 A 2AAR 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.

Original languageEnglish
Pages (from-to)672-680
Number of pages9
JournalInternational Journal of Cardiology
Issue number3
Publication statusPublished - 1 Jul 2013


Cite this

Reichelt, M. E., Ashton, K. J., Tan, X. L., Mustafa, S. J., Ledent, C., Delbridge, L. M. D., ... Morrison, R. R. (2013). The adenosine A2A receptor - Myocardial protectant and coronary target in endotoxemia. International Journal of Cardiology, 166(3), 672-680.