BACKGROUND: Dipeptidylpeptidase-4 inhibition is reported to have beneficial effects on myocardial ischemia. Mechanisms might include a reduced degradation of stromal cell-derived factor-1 alpha with subsequent increased recruitment of circulating stem cells and/or incretin receptor-dependent pathways. This study evaluated the novel xanthine-based dipeptidylpeptidase-4 inhibitors linagliptin (BI 1356) and BI 14361 in cardiac ischemia. METHODS: Male Wistar rats were pretreated with linagliptin or BI 14361 and subjected to ligation of the left anterior descending coronary artery for 30 min. RESULTS: Dipeptidylpeptidase-4 inhibition significantly reduced the infarct size after 7 days (-27.7%, p<0.05) and 8 weeks (-18.0%, p<0.05). There was a significantly improved maximum rate of left ventricular pressure decline (dP/dt min) in linagliptin-treated animals 8 weeks after ischemia/reperfusion. Apart from that, treatment did not improve cardiac function as determined by echocardiography and cardiac catheterization. Immunohistological staining revealed an increased number of cells positive for stromal cell-derived factor-1 alpha, CXCR-4 and CD34 within and around the infarcted area of BI 14361-treated animals. CONCLUSIONS: Linagliptin and BI 14361 are able to reduce infarct size after myocardial ischemia. The immunohistological findings support the hypothesis that dipeptidylpeptidase-4 inhibition via reduced cleavage of stromal cell-derived factor-1 alpha might lead to an enhanced recruitment of CXCR-4+ circulating progenitor cells.
BACKGROUND:Dipeptidylpeptidase-4 inhibition is reported to have beneficial effects on myocardial ischemia. Mechanisms might include a reduced degradation of stromal cell-derived factor-1 alpha with subsequent increased recruitment of circulating stem cells and/or incretin receptor-dependent pathways. This study evaluated the novel xanthine-based dipeptidylpeptidase-4 inhibitors linagliptin (BI 1356) and BI 14361 in cardiac ischemia. METHODS: Male Wistar rats were pretreated with linagliptin or BI 14361 and subjected to ligation of the left anterior descending coronary artery for 30 min. RESULTS:Dipeptidylpeptidase-4 inhibition significantly reduced the infarct size after 7 days (-27.7%, p<0.05) and 8 weeks (-18.0%, p<0.05). There was a significantly improved maximum rate of left ventricular pressure decline (dP/dt min) in linagliptin-treated animals 8 weeks after ischemia/reperfusion. Apart from that, treatment did not improve cardiac function as determined by echocardiography and cardiac catheterization. Immunohistological staining revealed an increased number of cells positive for stromal cell-derived factor-1 alpha, CXCR-4 and CD34 within and around the infarcted area of BI 14361-treated animals. CONCLUSIONS:Linagliptin and BI 14361 are able to reduce infarct size after myocardial ischemia. The immunohistological findings support the hypothesis that dipeptidylpeptidase-4 inhibition via reduced cleavage of stromal cell-derived factor-1 alpha might lead to an enhanced recruitment of CXCR-4+ circulating progenitor cells.
Authors: Annayya R Aroor; James R Sowers; Guanghong Jia; Vincent G DeMarco Journal: Am J Physiol Heart Circ Physiol Date: 2014-08-15 Impact factor: 4.733
Authors: Annayya Aroor; Susan McKarns; Ravi Nistala; Vincent DeMarco; Michael Gardner; Mariana Garcia-Touza; Adam Whaley-Connell; James R Sowers Journal: Cardiorenal Med Date: 2013-03-16 Impact factor: 2.041