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. Author manuscript; available in PMC: 2017 Nov 1.
Published in final edited form as: Basic Res Cardiol. 2016 Sep 19;111(6):62. doi: 10.1007/s00395-016-0583-0

Figure 7. Schematic mechanism of the cardio-splenic signaling axis in acute myocardial I/R injury.

Figure 7

1) Necrotic cardiomyocytes release HMGB1 into the bloodstream upon reperfusion, 2) HMGB1 activates splenic neutrophils by stimulating RAGE, 3) activated splenic neutrophils enter the bloodstream, and 4) circulating splenic neutrophils transmigrate to the ischemic myocardium guided by HMGB1 and/or other chemokine gradients.