Bradykinin attenuates endothelial-mesenchymal transition following cardiac ischemia-reperfusion injury.

Endothelial-mesenchymal transition (EndMT) is a crucial pathological process contributing to cardiac fibrosis. Bradykinin has been found to protect the heart against fibrosis. Whether bradykinin regulates EndMT has not been determined. Rats were subjected to ligation of the left anterior descending coronary artery for 1 h and subsequent reperfusion to induce cardiac ischemia-reperfusion (IR) injury. Bradykinin (0.5 μg/h) was infused by an osmotic pump implanted subcutaneously at the onset of reperfusion. Fourteen days later, the functional, histological, and molecular analyses were performed to investigate the changes in cardiac fibrosis and EndMT. Human coronary artery endothelial cells were utilized to determine the molecular mechanisms in vitro. Bradykinin treatment improved cardiac function and decreased fibrosis following cardiac IR injury, accompanied by ameliorated EndMT and increased nitric oxide (NO) production. In vitro experiments found that bradykinin mitigated transforming growth factor β1 (TGFβ1)-induced EndMT. Significantly, the bradykinin B 2 receptor antagonist or endothelial nitric oxide synthase inhibitor abolished the effects of bradykinin on EndMT inhibition, indicating that the bradykinin B 2 receptor and NO might mediate the effects of bradykinin on EndMT inhibition. Bradykinin plays an essential role in the process of cardiac fibrosis. Bradykinin preserves the cellular signature of endothelial cells, preventing them from EndMT following cardiac IR injury, possibly mediated by bradykinin B 2 receptor activation and NO production. • Bradykinin attenuates cardiac fibrosis after myocardial ischemia-reperfusion injury. • Bradykinin inhibits endothelial-mesenchymal transition in the heart. • Bradykinin inhibits endothelial-mesenchymal transition via promoting NO production. [ABSTRACT FROM AUTHOR]