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Biological Functions and Clinical Prospects of Extracellular Non-Coding RNAs in Diabetic Cardiomyopathy: an Updated Review

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Abstract

Diabetic cardiomyopathy (DCM) is one of the major causes of heart failure in diabetic patients. However, the pathogenesis of diabetic cardiomyopathy has not been fully elucidated. Diagnosis and therapeutic strategy of DCM is still challenging. Various non-coding RNAs (ncRNA) are implicated in the onset and progression of DCM. Interestingly, ncRNAs not only are regulators intracellularly, but also can exist and function in extracellular space. Recent evidences have demonstrated that extracellular ncRNAs play emerging roles in both intracardiac and inter-organ communication during the pathogenesis of DCM; thus, extracellular ncRNAs are attractive diagnostic biomarkers and potential therapeutic targets for DCM. This article will review the current knowledge of the roles of extracellular ncRNAs in DCM, especially focusing on their physio-pathological properties and perspectives of potential clinical translation for biomarkers and therapies.

Graphical abstract

Recent evidences have demonstrated that extracellular ncRNA play emerging roles in both intracardiac and inter-organ communication involved in the pathogenesis of diabetic cardiomyopathy (DCM), thus shown as attractive diagnostic biomarkers and potential therapeutics for DCM. In the current review, we first summarize the progress regarding the paracrine role of extracellular ncRNA in DCM. miRNAs and circRNAs have been shown to mediate the communication among cardiomyocytes, endothelial cells, and vascular smooth muscle cells in the diabetic heart. Subsequently, we systematically describe that extracellular ncRNAs contribute to the crosstalk between the heart and other organs in the context of diabetes. Researches have indicated that miRNAs acted as hepatokines and adipokines to mediates the injure effect of distal organs on hearts. As for clinical application, extracellular ncRNAs are promising biomarker and have therapeutic potential. (Created with BioRender.com)

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Abbreviations

DCM:

Diabetic cardiomyopathy

ncRNA:

Non-coding RNAs

DM:

Diabetes mellitus

HF:

Heart failure

CHD:

Coronary heart disease

DPP-4:

Dipeptidylpeptidase-4

GLP-1:

Glucagon-like peptide-1

SGLT2:

Sodium-dependent glucose transporters 2

lncRNA:

Long ncRNA

miRNA:

MicroRNA

siRNA:

Short interfering RNA

snoRNA:

Small nuclear RNA

piRNA:

Piwi-interacting RNA

ECM:

Extracellular matrix

EVs:

Extracellular vesicles

MVB:

Multi-vesicular body

T2D:

Type 2 diabetes

MCECs:

Mouse cardiac endothelial cells

CMR:

Cardiac magnetic resonance

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Funding

This work was supported by grants from the National Natural Science Foundation of China (nos. 81822002, 31771264, and 82100375). The funders had no role in the study design, data collection and analysis, manuscript preparation, or decision to publish.

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Authors and Affiliations

  1. Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, China

    Zhongwei Yin

  2. Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave., Wuhan, 430030, China

    Chen Chen

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Yin, Z., Chen, C. Biological Functions and Clinical Prospects of Extracellular Non-Coding RNAs in Diabetic Cardiomyopathy: an Updated Review. J. of Cardiovasc. Trans. Res. 15, 469–476 (2022). https://doi.org/10.1007/s12265-022-10217-0

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