TY  - JOUR
A1  - Hocher, Berthold
A1  - Sharkovska, Yuliya
A1  - Mark, Michael
A1  - Klein, Thomas
A1  - Pfab, Thiemo
T1  - The novel DPP-4 inhibitors linagliptin and BI 14361 reduce infarct size after myocardial ischemia/reperfusion in rats
JF  - International journal of cardiology
N2  - 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.
KW  - Dipeptidylpeptidase-4
KW  - Stromal cell-derived factor-1
KW  - Cardiac ischemia/reperfusion
KW  - Myocardial ischemia
KW  - Infarct size
KW  - Rats
Y1  - 2013
U6  - https://doi.org/10.1016/j.ijcard.2011.12.007
SN  - 0167-5273
VL  - 167
IS  - 1
SP  - 87
EP  - 93
PB  - Elsevier
CY  - Clare
ER  -