The Cardioprotective Effect of HIF-1[alpha]/miR-21/PDCD4 Pathway During Transplanted Heart Cold Storage

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays a major role under hypoxia condition. Cold storage during heart transplantation causes the donor heart long-term hypoxia. There are some evidence indicating a conceivable HIF-1α/miR-21/PDCD4 pathway. We assessed the hypothesis that Hypoxia-inducible factor -1α (HIF-1α) has a cardioprotective effect during donor heart cold storage, by making the miR-21 upregulate reduce the expression of PDCD4. We establish the rats heart cold storage model and stratified into 6-hour groups from 0 to 24 hours. Western blot and RT-qPCR were performed to detected the expression of HIF-1α, miR-21, PDCD4 and PTEN. After cold storage the expression of HIF-1α increased from 0 to 6 hours, then gradually decreased but the expression level was relatively higher compared to control group. The miR-21 was upregulated from 0 to 12 hous then downregulated. The mRNA expression of PDCD4 was upregulated gradually, but the protein expression was significantly downregulated in the 12 hour then continued to upregulate. Interestingly, the expression level of miR-21 was highest in the 12 hour, which indicated miR-21 could inhibite the PDCD4. And we subsequently detected the mRNA of PTEN which can inhibit the HIF-1α and be inhibited by miR-21.The expression of PTEN was also significantly downregulated in the 12 hour. In conclusion, there is possible interaction between HIF-1α and miR-21, and the conceivable HIF-1α/miR-21/PDCD4 pathway play a protective role in cold storage of heart. Key words: Heart Transplantation, Cold storage, miR-21, HIF-1α, PDCD4