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Olof Gidlöf

Research project participant

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Increased expression of miR-224-5p in circulating extracellular vesicles of patients with reduced coronary flow reserve


  • Kreema James
  • Paulina Bryl-Gorecka
  • Björn Olde
  • Olof Gidlof
  • Kristina Torngren
  • David Erlinge

Summary, in English

Background: Endothelial and microvascular dysfunction are pivotal causes of major adverse cardiac events predicted by coronary flow reserve (CFR). Extracellular Vesicles (EVs) have been studied extensively in the pathophysiology of coronary artery disease. However, little is known on the impact of the non-coding RNA content of EVs with respect to CFR. Methods: We carried out a study among 120 patients divided by high-CFR and low-CFR to profile the miRNA content of circulating EVs. Results: A multiplex array profiling on circulating EVs revealed mir-224-5p (p-value ≤ 0.000001) as the most differentially expressed miRNA in the Low-CFR group and showed a significantly independent relationship to CFR. Literature survey indicated the origin of the miR from liver cells and not of platelet, leukocyte, smooth muscle or endothelial (EC) origin. A q-PCR panel of the conventional cell type-EVs along with hepatic EVs showed that EVs from liver cells showed higher expression of the miR-224-5p. FACS analysis demonstrated the presence of liver-specific (ASGPR-1+/CD14−) EVs in the plasma of our cohort with the presence of Vanin-1 required to enter the EC barrier. Hepatic EVs with and without the miR-224-5p were introduced to ECs in-vitro, but with no difference in effect on ICAM-1 or eNOS expression. However, hepatic EVs elevated endothelial ICAM-1 levels per se independent of the miR-224-5p. Conclusion: This indicated a role of hepatic EVs identified by the miR-224-5p in endothelial dysfunction in patients with Low CFR.


  • Molecular Cardiology
  • Cardiology
  • Cardiovascular Epigenetics
  • Molecular Epidemiology and Cardiology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Teachers at the Medical Programme

Publishing year





BMC Cardiovascular Disorders





Document type

Journal article


BioMed Central (BMC)


  • Cardiac and Cardiovascular Systems


  • Cardiovascular disease
  • Coronary flow reserve
  • Extracellular vesicles
  • Hepatic
  • Major adverse cardiac events
  • Micro-RNA



Research group

  • Molecular Cardiology
  • Cardiovascular Epigenetics
  • Molecular Epidemiology and Cardiology


  • ISSN: 1471-2261