Renzo Grupper, Ross Edward, Christian Walter, Eva Varnous
Abstract
Myocardial ischemia reperfusion injury is a major problem in heart transplantation and its mechanism is still not fully known. MicroRNAs (miRNAs) are small, single-stranded RNA molecules which play an important role in posttranscriptional regulation of gene expression by inhibiting translation of target mRNAs. The objective of this study is to investigate the mechanistic role of miRNAs on global myocardial ischemia-reperfusion injury in mice. The mice heart was mounted in a Langendorff-type isolated heart perfusion system. The coronary effluent volume was measured at the various time intervals for a total of 120 min. Coronary flow rate (CFR, in ml · min−1 · g−1) was defined as the total volume collected during the reperfusion interval divided by the time, normalized by the heart wet weight (g), which was measured at the beginning of the experiment. The volume fraction of interstitial space (VFITS) in myocardial tissue was determined from H-E-stained sections by using the equation VFITS = (100% × area of interstitial space)/total tissue area. The mitochondrial cross-sectional area was measured. The number of fragmented mitochondria, the number of mitochondria with amorphous matrix densities or granular densities, and the total number of mitochondria studied in each group were counted. Further, The average LV dP/dt during 0–30, 30–60, 60–90, and 90–120 min of reperfusion was calculated from data continuously recorded during the corresponding reperfusion period. In conclusion the present data show that the miRNAs have a great potential as biomarker, therapeutic target, and led to significant new insights into the pathophysiology of global myocardial I/R, graft rejection.
Keywords: Myocardial ischemia reperfusion injury; Heart transplantation; MicroRNAs; Coronary flow rate
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