Objectives: 

The mechanisms of cardiac protection induced by Urocortin (Ucn) from ischemia/reperfusion injury have a high interest due to possible clinical applications. The objective of this study is to evaluate the long-term effects of Ucn in cell survival and regulation of this process through microRNAs.

Materials: 

We used Langendorff perfused rat hearts to determine hemodynamics parameters. Perfused hearts were subjected to ischemia/reperfusion (I/R) protocol and the cardioprotective effect of Ucn applied at the onset of reperfusion was characterized. We performed a microarray of microRNAs in samples from hearts submitted to I/R and from those treated with Ucn. We used quantitative PCR (qRT-PCR) to statistically validate the microRNAs candidates in cardiac protection by Ucn.

Results: 

Ucn infusion at the onset of reperfusion fully recovered hearts contractility; (dP/dt = 109.95 ± 6.89% in Ucn treated hearts vs 62.38 ± 6.84% in hearts submitted to I/R.) The array of microRNAs revealed a number of microRNAs that were expressed differently in the Ucn-treated hearts compared with control hearts. These results were validated by qRT-PCR for miR-29a, miR-499, miR-30c with a statistical significance at p<0,05. The analysis of array and qRT-PCR data determined that Ucn application in reperfusion prevented miR-29a and miR-499 alteration and maintained their expression in basal levels before the insult of I/R.

Conclusions: 

Our preliminary data show that Ucn applied during the first minutes on reperfusion allows a full recovery of ventricular function; and also promotes recovery of normal levels of microRNAs deregulated by the I/R injuries, such as miR-29a and miR-499. We suggest that long-term effects of Ucn could be mediated by microRNAs, which mediate genes regulation, which are necessary to reduce cell death mechanism like apoptosis and promote cell survival. Altogether indicate that microRNAs would be a good tool to modulate the protective mechanism against I/R syndrome and to improve the long-term cardiac remodeling that lead to heart failure.