In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.


The free consultation period for this content is over.

It is now only available year-round to ESC Professional Members, Fellows of the ESC, and Young combined Members

Extracellular Vesicle-incorporated Long Noncoding RNA PUNISHER as a novel biomarker and effector of vascular function

Session Blockbusters from the Young in Basic Science

Speaker Qian Li

Congress : ESC Congress 2019

  • Topic : basic science
  • Sub-topic : Basic Science - Vascular Biology and Physiology: Microvesicles, Exosomes
  • Session type : Abstract Session
  • FP Number : 2289

Authors : Q Li (Bonn,DE), YY Liu (Bonn,DE), MR Hosen (Bonn,DE), P Levermann (Bonn,DE), A Flender (Bonn,DE), E Latz (Bonn,DE), G Nickenig (Bonn,DE), N Werner (Bonn,DE), F Jansen (Bonn,DE)

Authors:
Q Li1 , YY Liu1 , MR Hosen1 , P Levermann1 , A Flender1 , E Latz1 , G Nickenig1 , N Werner1 , F Jansen1 , 1University Hospital Bonn - Bonn - Germany ,

Citation:

Background:

Circulating long noncoding RNAs (lncRNAs) have emerged as biomarkers and regulators in cardiovascular diseases. Whether small extracellular vesicles (sEV)-incorporated lncRNAs expression is regulated in coronary artery disease (CAD) is largely unknown. We aimed to explore the expression of plasma sEV-lncRNAs in patients with and without CAD as well as elucidate specific cellular function of sEV-incorporated lncRNA PUNISHER (also known as AGAP2-AS1) in vascular endothelial cells.

Methods and results:

We quantified the expression level of 13 cardiac- or atherosclerosis-related lncRNAs by quantitative real-time PCR (qRT-PCR) in plasma sEV from 6 stable CAD, 6 ACS and 6 non-CAD (NCAD) patients. 4 lncRNAs showing stable expression (PUNISHER, GAS5, MALAT1, and H19) were further evaluated in the validation study including 65 stable CAD, 43 ACS and 42 NCAD patients. Among those, PUNISHER was significantly increased in patients with stable CAD and ACS compared to NCAD. Area under the curve (AUC) value was 0.7 for stable CAD and 0.8 for ACS respectively, suggesting plasma sEV-PUNISHER as a potential diagnostic biomarker for CAD. In vitro, atherosclerotic stimuli consisting of oxLDL or TNF-a treatment upregulated PUNISHER level in human coronary artery endothelial cell (HCAEC) and in corresponding sEV in a dose-dependent way. Mechanistically, RNA immunoprecipitation (RIP) assay identified hnRNPK as an interaction partner of PUNISHER regulating its packaging into sEV. In vitro, endothelial-derived sEV were internalized into recipient ECs and transported incorporated PUNISHER into recipient cells promoting an angiogenic response. Mechanical downstream analysis using PCR array showed that sEV-mediated PUNISHER transfer altered expression of vascular endothelial growth factor A (VEGFA) in recipient ECs.

Conclusion:

This translational study highlights sEV-incorporated lncRNA PUNISHER as biomarker and effector in vascular disease.



Based on your interests

Members get more

Join now
  • 1ESC Professional Members – access all resources from ESC Congress and ESC Asia with APSC & AFC
  • 2ESC Association Members (Ivory, Silver, Gold) – access your Association’s congress resources
  • 3Under 40 or in training - with a Combined Membership, access resources from all congresses
Join now

Our sponsors

ESC 365 is supported by Bayer, Boehringer Ingelheim and Lilly Alliance, Bristol-Myers Squibb and Pfizer Alliance, Novartis Pharma AG and Vifor Pharma in the form of educational grants. The sponsors were not involved in the development of this platform and had no influence on its content.

logo esc

Our mission: To reduce the burden of cardiovascular disease

Who we are