Journal article

Publication year: 2020

Pages: 5528-5541

Journal: Journal of Cellular and Molecular Medicine

Volume number: 24

Issue number: 10

ISSN: 1582-1838

eISSN: 1582-4934

Open access status: Gold

DOI Link: https://doi.org/10.1111/jcmm.15209

Publisher: Wiley

Abstract: 
Ischaemic post-conditioning (IPoC) is a clinical applicable procedure to reduce reperfusion injury. Non-responsiveness to IPoC possibly caused by co-morbidities limits its clinical attractiveness. We analysed differences in the expression of mitochondrial proteins between IPoC responder (IPoC-R) and non-responder (IPoC-NR). Eighty rats were randomly grouped to sham, ischaemia/reperfusion (I/R), IPoC or ischaemic pre-conditioning (IPC, as positive cardioprotective intervention) in vivo. Infarct sizes were quantified by plasma troponin I levels 60 minutes after reperfusion. After 7 days, rats were sacrificed and left ventricular tissue was taken for post hoc analysis. The transcriptome was analysed by qRT-PCR and small RNA sequencing. Key findings were verified by immunoblots. I/R increased plasma troponin I levels compared to Sham. IPC reduced troponin I compared to I/R, whereas IPoC produced either excellent protection (IPoC-R) or no protection (IPoC-NR). Twenty-one miRs were up-regulated by I/R and modified by IPoC. qRT-PCR analysis revealed that IPoC-R differed from other groups by reduced expression of arginase-2 and bax, whereas the mitochondrial uncoupling protein (UCP)-2 was induced in IPC and IPoC-R. IPoC-R and IPoC-NR synergistically increased the expression of non-mitochondrial proteins like VEGF and SERCA2a independent of the infarct size. Cardiac function was more closely linked to differences in mitochondrial proteins than on regulation of calcium-handling proteins. In conclusion, healthy rats could not always be protected by IPoC. IPoC-NR displayed an incomplete responsiveness which is reflected by different changes in the mitochondrial transcriptome compared to IPoC-R. This study underlines the importance of mitochondrial proteins for successful long-term outcome.

Harvard Citation style: Schreckenberg, R., Klein, J., Kutsche, H., Schulz, R., Gomori, K., Bencsik, P., et al. (2020) Ischaemic post-conditioning in rats: Responder and non-responder differ in transcriptome of mitochondrial proteins, Journal of Cellular and Molecular Medicine, 24(10), pp. 5528-5541. https://doi.org/10.1111/jcmm.15209

APA Citation style: Schreckenberg, R., Klein, J., Kutsche, H., Schulz, R., Gomori, K., Bencsik, P., Benczik, B., Agg, B., Saghy, E., Ferdinandy, P., & Schlueter, K. (2020). Ischaemic post-conditioning in rats: Responder and non-responder differ in transcriptome of mitochondrial proteins. Journal of Cellular and Molecular Medicine. 24(10), 5528-5541. https://doi.org/10.1111/jcmm.15209