Extracellular Vesicles and Endocannabinoid Signaling in Patients with COVID-19

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Florian Brandes - , Klinikum der Ludwig-Maximilians-Universität (LMU) München (Erstautor:in)
  • Annekathrin M Keiler - , Umweltmonitoring und Endokrinologie (FoG), Institut für Dopinganalytik und Sportbiochemie Dresden (Autor:in)
  • Benedikt Kirchner - , Klinikum der Ludwig-Maximilians-Universität (LMU) München (Autor:in)
  • Melanie Borrmann - , Klinikum der Ludwig-Maximilians-Universität (LMU) München (Autor:in)
  • Jean-Noël Billaud - , QIAGEN Digital Insights (Autor:in)
  • Marlene Reithmair - , Klinikum der Ludwig-Maximilians-Universität (LMU) München (Autor:in)
  • Matthias Klein - , Klinikum der Ludwig-Maximilians-Universität (LMU) München (Autor:in)
  • Patrizia Campolongo - , University of Rome La Sapienza (Autor:in)
  • Detlef Thieme - , Institut für Dopinganalytik und Sportbiochemie Dresden (Autor:in)
  • Michael W Pfaffl - (Autor:in)
  • Gustav Schelling - , Klinikum der Ludwig-Maximilians-Universität (LMU) München (Autor:in)
  • Agnes S Meidert - , Klinikum der Ludwig-Maximilians-Universität (LMU) München (Letztautor:in)


Introduction: Endocannabinoids in COVID-19 have immunomodulatory and anti-inflammatory properties but the functional role and the regulation of endocannabinoid signaling in this pandemic disorder is controversial. To exercise their biologic function, endocannabinoids need to travel across the intercellular space and within the blood stream to reach their target cells. How the lipophilic endocannabinoids are transported in the vascular system and how these hydrophobic compounds cross cell membranes is still unclear. Extracellular vesicles (EVs) are released and incorporated by many cell types including immune cells. EVs are small lipid-membrane covered particles and contain RNA, lipids and proteins. They play an important role in intercellular communication by transporting these signaling molecules from their cells of origin to specific target cells. EVs may represent ideal transport vehicles for lipophilic signaling molecules like endocannabinoids and this effect could also be evident in COVID-19. Materials and Methods: We measured the endocannabinoids anandamide, 2-AG, SEA, PEA and OEA in patients with COVID-19 in EVs and plasma. RNA sequencing of microRNAs (miRNAs) derived from EVs (EV-miRNAs) and mRNA transcripts from blood cells was used for the construction of signaling networks reflecting endocannabinoid and miRNA communication by EVs to target immune cells. Results: With the exception of anandamide, endocannabinoid concentrations were significantly enriched in EVs in comparison to plasma and increased with disease severity. No enrichment in EVs was seen for the more hydrophilic steroid hormones cortisol and testosterone. High EV-endocannabinoid concentrations were associated with downregulation of CNR2 (CB2) by upregulated EV-miRNA miR-146a-5p and upregulation of MGLL by downregulated EV-miR-199a-5p and EV-miR-370-5p suggesting counterregulatory effects. In contrast, low EV-levels of anandamide were associated with upregulation of CNR1 by downregulation of EV-miR-30c-5p and miR-26a-5p along with inhibition of FAAH. Immunologically active molecules in immune cells regulated by endocannabinoid signaling included VEGFA, GNAI2, IGF1, BDNF, IGF1R and CREB1 and CCND1 among others. Discussion and Conclusions: EVs carry immunologically functional endocannabinoids in COVID-19 along with miRNAs which may regulate the expression of mRNA transcripts involved in the regulation of endocannabinoid signaling and metabolism. This mechanism could fine-tune and adapt endocannabinoid effects in recipient cells in relationship to the present biological context.


FachzeitschriftCannabis and cannabinoid research
PublikationsstatusElektronische Veröffentlichung vor Drucklegung - 14 Sept. 2023

Externe IDs

ORCID /0000-0002-2157-4711/work/142660244
unpaywall 10.1089/can.2023.0040
Scopus 85172385226