Myocardial pressure overload induces systemic inflammation through endothelial cell IL-33

The association of hypertension and inflammation is clear, but mechanisms for this human finding remain elusive. The experiments in this article demonstrate that a highly local intramyocardial signaling pathway through ST2, the receptor for the proinflammatory cytokine interleukin 33 (IL-33), regulates the heart’s response to pressure overload. By generating and using new conditional deletion mice, we identified endothelial cells as the major source of systemic circulating IL-33. Our study reveals that endothelial cell secretion of IL-33 is crucial for translating myocardial pressure overload into a selective systemic inflammatory state.