Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells.

Publisher: BioMed Central Country of Publication: England NLM ID: 101147637 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2840 (Electronic) Linking ISSN: 14752840 NLM ISO Abbreviation: Cardiovasc Diabetol Subsets: MEDLINE

Original Publication: London : BioMed Central, [2002-

Biomarkers*/metabolism ; Diabetes Mellitus*/metabolism ; Exosomes*/genetics ; Exosomes*/metabolism ; MicroRNAs*/metabolism; Animals ; Humans ; Mice ; Endothelial Cells/metabolism ; Fatty Acids/metabolism ; Glucose/metabolism ; In Situ Hybridization, Fluorescence

Background: Coronary microvascular dysfunction (CMD) is a frequent complication of diabetes mellitus (DM) characterized by challenges in both diagnosis and intervention. Circulating levels of microRNAs are increasingly recognized as potential biomarkers for cardiovascular diseases.
Methods: Serum exosomes from patients with DM, DM with coronary microvascular dysfunction (DM-CMD) or DM with coronary artery disease (DM-CAD) were extracted for miRNA sequencing. The expression of miR-16-2-3p was assessed in high glucose-treated human aortic endothelial cells and human cardiac microvascular endothelial cells. Fluorescence in situ hybridization (FISH) was used to detect miR-16-2-3p within the myocardium of db/db mice. Intramyocardial injection of lentivirus overexpressing miR-16-2-3p was used to explore the function of the resulting gene in vivo. Bioinformatic analysis and in vitro assays were carried out to explore the downstream function and mechanism of miR-16-2-3p. Wound healing and tube formation assays were used to explore the effect of miR-16-2-3p on endothelial cell function.
Results: miR-16-2-3p was upregulated in circulating exosomes from DM-CMD, high glucose-treated human cardiac microvascular endothelial cells and the hearts of db/db mice. Cardiac miR-16-2-3p overexpression improved cardiac systolic and diastolic function and coronary microvascular reperfusion. In vitro experiments revealed that miR-16-2-3p could regulate fatty acid degradation in endothelial cells, and ACADM was identified as a potential downstream target. MiR-16-2-3p increased cell migration and tube formation in microvascular endothelial cells.
Conclusions: Our findings suggest that circulating miR-16-2-3p may serve as a biomarker for individuals with DM-CMD. Additionally, miR-16-2-3p appears to alleviate coronary microvascular dysfunction in diabetes by modulating ACADM-mediated fatty acid degradation in endothelial cells.
(© 2024. The Author(s).)

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ZKX20018 Special Fund of Health Science and Technology of Nanjing

Keywords: Coronary microvascular dysfunction; Diabetes; Exosomes; Microvascular endothelial cells; miR-16-2-3p

0 (Biomarkers)
0 (Fatty Acids)
IY9XDZ35W2 (Glucose)
0 (MicroRNAs)
0 (MIRN16 microRNA, human)

Date Created: 20240209 Date Completed: 20240214 Latest Revision: 20240625

20240625

PMC10858495

10.1186/s12933-024-02142-0

38336726