Renal Damage after Myocardial Infarction is Prevented by Linagliptin, a Dipeptidyl Peptidase Inhibitor, for Cardio-renal Protection

Myocardial infarction (MI) aggravates preexistent mild renal damage that is elicited by unilateral nephrectomy in rats. However, cardio-renal protection after MI is unclear. We evaluate whether linagliptin, a dipeptidyl peptidase inhibitor, improves cardiovascular remodeling and renal damage after MI in unilateral nephrectomized (UNX) Wistar rats. MI was induced after UNX by ligation of the left coronary artery (UMI). Vehicle and linagliptin were administration in UMI rats for 12 weeks. Impaired glomerulosclerosis and interstitial fibrosis in UMI rats were ameliorated by linagliptin. Podocyte injury such as decreased expression of nephrin and podocin and increased desmin-positive area in the renal cortex of UMI rats were restored by linagliptin. Upregulation of tumor necrosis factor-alpha expression and nuclear factor-kappaB phosphorylation and CD68-positive area in the renal cortex were suppressed by linagliptin. Decreased %FS and increased fibrosis area in the LV was improved by linagliptin. UMI rats in the renal cortex and LV were characterized by increased NAD(P)H oxidase p22phox, p47phox, gp91phox, and decreased eNOS phosphorylation, and linagliptin improved these indices. These findings suggest that cardio-renoprotective effect of linagliptin in cardio-renal damage after MI may play an important role in UMI rats. Thus, linagliptin may be a therapeutic strategy in the kidney and heart after MI.