Abstract 453: The Role of PD-1/PDL-1 in Myocardial Ischemia Reperfusion Injury.
Programmed Death-1 (PD-1) and its ligand, PDL-1, are expressed on immune cells and have emerged as negative regulators of immune and inflammatory mechanisms. Aside from the contribution of systemic immune and inflammatory mechanisms to myocardial ischemia reperfusion (IR) injury, isolated heart studies have shown that the myocardium is capable of mounting a robust inflammatory response to an IR insult. However, potential involvement of PD-1/PDL-1 in the setting of cardiac IR injury is not established. We tested the hypothesis that an IR insult downregulates PD-1/PDL-1 pathway thereby exacerbating the inflammatory response and cell death. According, Langendorff-perfused rat hearts were subjected to 40 min of ischemia and 15 min of reperfusion; normoxic hearts served as controls. Thereafter, cardiac cells were prepared and subjected to flow-cytometry-based assays. The ischemic-reperfused hearts displayed a marked increase in the pro-inflammatory cytokine interleukin-17 in association with disruption of mitochondrial membrane potential (JC-1 assay) and apoptotic and necrotic cell death. Importantly, the ischemic-reperfused hearts showed a significant increase in PD-1 and PDL-1 positive cells. The results suggest that cardiac PD-1/ PDL-1 pathway likely constitutes an endogenous mechanism whose upregulation in the ischemic-reperfused heart curbs the inflammatory response and associated tissue injury.
- © 2012 by American Heart Association, Inc.