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Overexpression of miR-199b-5p in Colony Forming Unit-Hill’s Colonies Positively Mediates the Inflammatory Response in Subclinical Cardiovascular Disease Model: Metformin Therapy Attenuates Its Expression

Lookup NU author(s): Dr Sherin Bakhashab, Rosie Barber, Josie O'Neill, Dr Catherine ArdenORCiD, Dr Jolanta Weaver

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2024 by the authors.Well-controlled type 1 diabetes (T1DM) is characterized by inflammation and endothelial dysfunction, thus constituting a suitable model of subclinical cardiovascular disease (CVD). miR-199b-5p overexpression in murine CVD has shown proatherosclerotic effects. We hypothesized that miR-199b-5p would be overexpressed in subclinical CVD yet downregulated following metformin therapy. Inflammatory and vascular markers were measured in 29 individuals with T1DM and 20 matched healthy controls (HCs). miR-199b-5p expression in CFU-Hill’s colonies was analyzed from each study group, and correlations with inflammatory/vascular health indices were evaluated. Significant upregulation of miR-199b-5p was observed in T1DM, which was significantly downregulated by metformin. miR-199b-5p correlated positively with vascular endothelial growth factor-D and c-reactive protein (CRP: nonsignificant). ROC analysis determined miR-199b-5p to define subclinical CVD by discriminating between HCs and T1DM individuals. ROC analyses of HbA1c and CRP showed that the upregulation of miR-199b-5p in T1DM individuals defined subclinical CVD at HbA1c > 44.25 mmol and CRP > 4.35 × 106 pg/mL. Ingenuity pathway analysis predicted miR-199b-5p to inhibit the target genes SIRT1, ETS1, and JAG1. Metformin was predicted to downregulate miR-199b-5p via NFATC2 and STAT3 and reverse its downstream effects. This study validated the antiangiogenic properties of miR-199b-5p and substantiated miR-199b-5p overexpression as a biomarker of subclinical CVD. The downregulation of miR-199b-5p by metformin confirmed its cardio-protective effect.

Publication metadata

Author(s): Bakhashab S, Barber R, O'Neill J, Arden C, Weaver JU

Publication type: Article

Publication status: Published

Journal: International Journal of Molecular Sciences

Year: 2024

Volume: 25

Issue: 15

Print publication date: 01/08/2024

Online publication date: 25/07/2024

Acceptance date: 21/07/2024

Date deposited: 20/08/2024

ISSN (print): 1661-6596

ISSN (electronic): 1422-0067

Publisher: Multidisciplinary Digital Publishing Institute (MDPI)

URL: https://doi.org/10.3390/ijms25158087

DOI: 10.3390/ijms25158087

Data Access Statement: The original contributions presented in the study are included in the article; further inquiries can be directed to the corresponding author.

PubMed id: 39125657

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