Interleukin-10 attenuates renal injury after myocardial infarction in diabetes

Acute kidney injury (AKI) is a common complication after myocardial infarction (MI) and associated with significant morbidity and mortality. AKI after MI occurs more frequently in patients with diabetes, however, the underlying mechanisms are poorly understood, and specific treatments are lacking. Using the murine MI model, we show that diabetic mice had higher expression of the kidney injury marker, neutrophil gelatinase-associated lipocalin (NGAL), 3 days after MI compared with control mice. This higher expression of NGAL was still significant after controlling for differences in myocardial infarct size between diabetic and control mice. Prior data demonstrate increased cell-free hemoglobin after MI in diabetic mice. Therefore, we investigated heme clearance components, including heme oxygenase 1 (HO-1) and CD163, in the kidneys and found that both HO-1 and CD163 were dysregulated in diabetic mice pre-MI and post-MI. Significantly higher levels of urine iron were also observed in diabetic mice compared with control mice after MI. Next, the renal protective effect of interleukin 10 (IL-10) after MI was tested in diabetic MI. IL-10 treatment demonstrated multiple protective effects after diabetic MI including reduction in acute renal inflammation, upregulation of renal heme clearance pathways, attenuation of chronic renal fibrosis, and reduction in albuminuria after diabetic MI. In vitro, IL-10 potentiated hemoglobin-induced HO-1 expression in mouse bone marrow-derived macrop...

Source: Journal of Investigative Medicine - June 22, 2022 Category: Research Authors: Fan, X., Zhang, X., Liu, L. C., Kim, A. Y., Curley, S. P., Chen, X., Dworkin, L. D., Cooper, C. J., Gupta, R. Tags: Original research Source Type: research