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State of the Art - Functional importance of regulatory RNA species

ESC Congress Report

  • lncRNA are important in cardiovascular disease.
  • lncRNA are related to cardiac differentiation.
  • Fetal cardiac enhancers are reactivated after stress.

View the Slides from this session in ESC Congress 365

Non-coding regulatory RNA species are a large group of molecules, including small microRNAs, long-non-coding RNAs and many other RNA species, such as enhancer RNAs. In this session, which was well attended despite parallel ongoing hotline sessions, 6 speakers presented new data about the afore mentioned three non-coding RNA species and their role in cardiovascular development and (patho)biology.

The first speaker, Dr. Michael Alexanian from Lausanne, presented data about a long non-coding RNA CARMEN which was involved in cardiac development. After describing the different functions of lncRNAs (e.g. RNA decoy or miRNA sponging), he presented expression profiles of lncRNAs during differentiation of human cardiac precursor cells. The lncRNA CARMEN was expressed and upregulated during cardiac differentiation. A shRNA approach to decrease CARMEN prevented cardiac differentiation showing a functional role of this lncRNA.

Dr. Rudi Micheletti, also from Lausanne, presented data about cardiac enhancer-associated  non-coding RNAs during cardiac development and disease. Two of these ncRNAs MM67 and MM85 showed a similar pattern of expression such as myocardin during cardiac development. These two ncRNAs also had human orthologous. He also showed that fetal cardiac enhancers are reactivated after stress and thus could serve as interesting new therapeutic targets. Dr. Nishino from Kyoto presented data about miR-33a to regulate lipogenetic pathways in vivo. Liver ABCA1 and serum HDL-C levels were increased in miR-33 mice casting doubts about potential ongoing (long-term) therapeutic use of miR33 inhibitors.

Dr. Felix Janssen from Bonn showed data about endothelial microparticles (EMPs) and their effects on endothelial cell activation. This group showed that EMPs contain miRNAs such as MiR-222 that could be transferred to endothelial cells. EMP transfusion to mice reduced endothelial activation and atherosclerosis development. This might be due to transfer of selected miRNAs such as miR-222 opening a potential new therapeutic approach. Dr. Fiedler from Hannover, Germany used next generation RNA sequencing approaches to identify lncRNAs that are activated by hypoxia in human endothelial cells. He identified several candidates that were highly upregulated in endothelial cells after hypoxia. A particular transcript entitled HSLNCR-3 was of considerable importance. Silencing of this lncRNA led to decreased proliferation of endothelial cells in vitro, as well as impaired vascularization of an human engineered heart model, (in cooperation with Eschenhagen, Hamburg, Germany) showing potential therapeutic use of modulation of this lncRNA in ischemic diseases that require increased capillary density and blood supply.

Finally, Dr. Thomas Thum from Hannover gave a lecture presenting novel data on lncRNAs involved in the cardiac hypertrophy process and summarized the session for the audience. During discussions in this session it became clear that studies with lncRNAs in cardiovascular disease are of great importance as this new group of non-coding RNAs provide new mechanistic understanding and a new avenue of therapeutic options to treat cardiovascular disease.




State of the Art - Functional importance of regulatory RNA species

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.