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. 2025 Jan;182(2):417-431.
doi: 10.1111/bph.17329. Epub 2024 Oct 14.

miR-210 as a therapeutic target in diabetes-associated endothelial dysfunction

Aida Collado  1 , Tong Jiao  1 , Eftychia Kontidou  1 , Lucas Rannier Ribeiro Antonino Carvalho  2 , Ekaterina Chernogubova  3 , Jiangning Yang  1 , Germana Zaccagnini  4 , Allan Zhao  2 , John Tengbom  1 , Xiaowei Zheng  5 , Bence Rethi  5 , Michael Alvarsson  6 , Sergiu-Bogdan Catrina  6   7 , Ali Mahdi  1 , Mattias Carlström  2 , Fabio Martelli  4 , John Pernow  1   8 , Zhichao Zhou  1
Affiliations

miR-210 as a therapeutic target in diabetes-associated endothelial dysfunction

Aida Collado et al. Br J Pharmacol. 2025 Jan.

Abstract

Background and purpose: MicroRNA (miR)-210 function in endothelial cells and its role in diabetes-associated endothelial dysfunction are not fully understood. We aimed to characterize the miR-210 function in endothelial cells and study its therapeutic potential in diabetes.

Experimental approach: Two different diabetic mouse models (db/db and Western diet-induced), miR-210 knockout and transgenic mice, isolated vessels and human endothelial cells were used.

Key results: miR-210 levels were lower in aortas isolated from db/db than in control mice. Endothelium-dependent relaxation (EDR) was impaired in aortas from miR-210 knockout mice, and this was restored by inhibiting miR-210 downstream protein tyrosine phosphatase 1B (PTP1B), mitochondrial glycerol-3-phosphate dehydrogenase 2 (GPD2), and mitochondrial oxidative stress. Inhibition of these pathways also improved EDR in both diabetic mouse models. High glucose reduced miR-210 levels in endothelial cells and impaired EDR in mouse aortas, effects that were reversed by overexpressing miR-210. However, plasma miR-210 levels were not affected in individuals with type 2 diabetes (T2D) following improved glycaemic status. Of note, genetic overexpression using miR-210 transgenic mice and pharmacological overexpression using miR-210 mimic in vivo ameliorated endothelial dysfunction in both diabetic mouse models by decreasing PTP1B, GPD2 and oxidative stress. Genetic overexpression of miR-210 altered the aortic transcriptome, decreasing genes in pathways involved in oxidative stress. miR-210 mimic restored decreased nitric oxide production by high glucose in endothelial cells.

Conclusion and implications: This study unravels the mechanisms by which down-regulated miR-210 by high glucose induces endothelial dysfunction in T2D and demonstrates that miR-210 serves as a novel therapeutic target.

Linked articles: This article is part of a themed issue Non-coding RNA Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.2/issuetoc.

Keywords: endothelial dysfunction; high glucose; miR‐210; oxidative stress; type 2 diabetes.

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References

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