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

James, Kreema LU orcid ; Bryl-Gorecka, Paulina LU ; Olde, Björn LU ; Gidlof, Olof LU ; Torngren, Kristina LU and Erlinge, David LU orcid (2022) In BMC Cardiovascular Disorders 22(1).
Abstract

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... (More)

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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiovascular disease, Coronary flow reserve, Extracellular vesicles, Hepatic, Major adverse cardiac events, Micro-RNA
in
BMC Cardiovascular Disorders
volume
22
issue
1
article number
321
publisher
BioMed Central (BMC)
external identifiers
  • pmid:35850658
  • scopus:85134420690
ISSN
1471-2261
DOI
10.1186/s12872-022-02756-w
language
English
LU publication?
yes
id
eccc0ee2-eee1-468c-acec-eb5eca574509
date added to LUP
2022-09-15 13:03:16
date last changed
2025-03-17 23:22:09
@article{eccc0ee2-eee1-468c-acec-eb5eca574509,
  abstract     = {{<p>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.</p>}},
  author       = {{James, Kreema and Bryl-Gorecka, Paulina and Olde, Björn and Gidlof, Olof and Torngren, Kristina and Erlinge, David}},
  issn         = {{1471-2261}},
  keywords     = {{Cardiovascular disease; Coronary flow reserve; Extracellular vesicles; Hepatic; Major adverse cardiac events; Micro-RNA}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Cardiovascular Disorders}},
  title        = {{Increased expression of miR-224-5p in circulating extracellular vesicles of patients with reduced coronary flow reserve}},
  url          = {{http://dx.doi.org/10.1186/s12872-022-02756-w}},
  doi          = {{10.1186/s12872-022-02756-w}},
  volume       = {{22}},
  year         = {{2022}},
}