MicroRNA-100 - a protectice epigenetic player in ischemia-reperfusion injury

• Applicant: Dr. Franziska Pankratz
• Subject Area: Cardiology, Angiology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429138885

Ischemia reperfusion (IR) injury has clinical relevance in diverse fields of modern medicine, in which blood flow is interventionally or pharmaceutically restored after a longer period of ischemia, for example myocardial infarction or stroke. Reperfusion is associated with a local inflammatory response triggered by the damaged endothelium, inflammatory cytokines and activated leukocytes, resulting in disruption of the blood flow in postcapillary venules. The processes of I/R are not fully understood and in particular the role of the small non-coding microRNAs (miRNA) is largely unknown. MicroRNAs regulate gene expression on a post-transcriptional level and are involved in many biological processes and first studies indicate an important role of miRNAs also in myocardial infarction and inflammatory processes. We recently identified miR-100 as an anti-angiogenic and anti-inflammatory player in vascular cells. The latter by the regulation of heterocellular interaction of leukocytes and circulating cells via suppression of vascular adhesion molecules. We now aim to analyze the role of miR-100 in sterile inflammatory processes of ischemia reperfusion injury by employing two models of I/R namely intravital microscopy of the cremaster muscle and temporary occlusion of the LAD under different miR-100 expression conditions. A newly generated transgenic mouse strain allows the investigation of genetic miR-100 overexpression and in addition miR-100 expression will be modulated using specific synthetic antisense or precursor oligonucleotides in wildtype animals to prove the therapeutic potential of this miRNA. Our preliminary data suggest that miR-100 might be a powerful epigenetic modulator of ischemia reperfusion injury and the pharmacologically modulation of microRNA expression level might represent a new therapeutic option for the treatment of diseases based on I/R injury such as myocardial infarction and stroke and complications following organ and tissue transplantation.

• DFG Programme: Research Grants