Abstract 10741: Effects of Dual Stem Cell Therapy (g-csf+sitagliptin) On Cardiac Levels of Micrornas After Myocardial Infarction
Introduction: Ischemic cardiomyopathy may be prevented by myocardial regeneration after stem cell therapy. In former studies, we established a new dual therapeutic concept by combining pharmacological inhibition of DPP-IV (which stabilizes cardiac SDF-1) with G-CSF mediated stem cell mobilization after myocardial infarction (MI). This approach lead to 1) increased myocardial homing of circulating CXCR-4+ stem cells 2) stimulation of resident cardiac stem cells 3) improved heart function (Millar tip catheterization) and survival (Kaplan Meier curves).
Methods and Results: We induced acute MI in 10-11 weeks old male C57BL/6 mice using surgical occlusion of the left descending artery. Then, we gained cardiac tissue from the infarct area, border zone and the remote area and extracted RNA. In the first step, we ensured that the reference microRNAs SNORD69, SNORD85 and U6 correlated highly significantly thus the arithmetic mean of them served as reference for the further experiments. Six days after infarction, expression of cardiac microRNAs was assessed (using RT-PCR) in GCSF+Sitagliptin treated mice in comparison to several control groups (healthy animals; GCSF or Sitagliptin mono treatment or Saline application after MI). MicroRNA 92a (inhibiting neovascularization) and microRNA126 (controlling SDF-1 expression) were reduced in the infarct and border zone in all groups after MI whereas microRNA21 (promoting fibrosis) was enhanced in the infarct zones. However, there were no significant differences between the treatment regimens. In contrast, GCSF+Sitagliptin administration significantly reduced cardiac expression of microRNA155 which is known to be proinflammatory. This finding goes in parallel with the fact that GCSF+Sitagliptin reduced cardiac remodelling: 28 days after MI, since infarct area was reduced and left ventricular wall thickness was increased in the mice receiving dual stem cell therapy.
Conclusion: In addition to the known effects of dual stem cell therapy after MI we show for the first time that GCSF+Sitagliptin affect myocardial healing by the reduction of microRNA155 leading to decreased cardiac remodelling.
- © 2011 by American Heart Association, Inc.