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Circular RNAs: regulators of vascular smooth muscle cells in cardiovascular diseases

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Abstract

The aberrant expansion and dysfunction of vascular smooth muscle cells (VSMCs) contribute to the occurrence and development of many cardiovascular diseases. Circular RNAs, a new class of non-coding RNAs with the 3′ and 5′ ends covalently linked together due to back-splicing, have recently been revealed to function as new regulators of VSMCs. These circular RNAs mainly act as RNA sponge to downregulate other regulatory non-coding RNAs such as microRNAs, influencing the overgrowth and transformation of VSMCs under pathogenic conditions. The purpose of this review is to summarize how circular RNAs fluctuate their own expression in response to multiple stimuli in vitro and in vivo and how they modulate the phenotypic adaptation, proliferation, migration, apoptosis, and senescence of VSMCs, which in turn affects the progression of cardiovascular diseases. Finally, we highlight the potential of circular RNAs as the biomarkers and therapeutic targets for abnormal VSMCs and cardiovascular diseases.

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Abbreviations

VSMC:

Vascular smooth muscle cell

CVD:

Cardiovascular disease

ncRNA:

Non-coding RNA

miRNA:

MicroRNA

AS:

Atherosclerosis

circRNA:

Circular RNA

IA:

Intracranial aneurysm

AAA:

Abdominal aortic aneurysm

HPH:

Hypoxic pulmonary hypertension

ecircRNA:

Exonic circRNA

ciRNA:

Circular intronic circRNA

EIciRNA:

Exon intron circRNA

RIP:

RNA Immunoprecipitation

FISH:

Fluorescence in situ hybridization

qRT-PCR:

Quantitative real-time polymerase chain reaction

MCP-1:

Monocyte chemotactic protein-1

VCAM-1:

Vascular cell adhesion molecule-1

ICAM-1:

Intercellular cell adhesion molecule-1

SMMHC:

Cardiac myosin heavy chain

PTEN:

Phosphatase and tensin homolog

Ang II:

Angiotensin II

α-SMA:

α-Smooth muscle actin

Diaph3:

Diaphanous-related formin-3

Nrp1:

Neuropilin-1

IGF1R:

Insulin-like growth factor 1 receptor

PDGF-BB:

Platelet-derived growth factor-BB

HASMC:

Human aortic smooth muscle cell

SM22α:

Smooth muscle 22 alpha

HDAC5:

Histone deacetylase 5

Aggf1:

Angiogenic factors with G patch and FHA domains

MMP9:

Matrix metalloproteinase 9

OPN:

Osteopontin

TXNIP:

Thioredoxin-interacting protein

HCASMC:

Human coronary artery smooth muscle cell

CHD:

Coronary heart disease

AAV9:

Adeno-associated virus 9

TET2:

Ten-eleven translocation 2

5hmC:

5-Hydroxymethylcytosine

TGF-β:

Transforming growth factor-β

NRG-1:

Neuregulin-1

NRG-1-ICD:

Neuregulin-1 intracellular domain

PASMC:

Pulmonary arterial smooth muscle cell

CAMK2D:

Calcium/calmodulin-dependent kinase II-delta

CNN3:

Calponin 3

SYK:

Spleen associated tyrosine kinase

FOXO1:

Forkhead box protein O1

SP1:

Specificity protein 1

Myo10:

Myosin 10

HMGA2:

High mobility group AT-hook 2

PCNA:

Proliferating cell nuclear antigen

NRP2:

Neuropilin 2

HDAC4:

Histone deacetylase 4

VEGFA:

Vascular endothelial growth factors A

FGF1:

Fibroblast growth factor 1

ox-LDL:

Oxidized low density lipoprotein

STIM1:

Stromal interaction molecule 1

MASMC:

Mouse aortic smooth muscle cell

MECP2:

Methyl-CpG binding protein 2

RASA1:

Ras p21 protein activator 1

VEGFR-2:

Vascular endothelial growth factors receptor-2

GREM1:

Gremlin 1

MCL1:

Myeloid cell leukemia sequence 1

ROS:

Reactive oxygen species

CDK6:

Cyclin dependent kinase 6

FOXC1:

Forkhead transcription factor 1

PDCD6:

Programmed cell death protein 6

ILF3:

Interleukin enhancer-binding factor 3

CDK4:

Cyclin dependent kinase 4

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81371675).

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Authors and Affiliations

  1. Hengyang Medical School, University of South China, Hengyang, 410001, China

    Meichun Wu & Yu** Chen

  2. Institute of Pharmacy & Pharmacology, School of Pharmaceutical Science, University of South China, 28 West Changsheng Road, Hengyang Hunan, 410001, China

    Min Xun & Yu** Chen

  3. School of Nursing, University of South China, Hengyang, 410001, China

    Meichun Wu

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  1. Meichun Wu
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  2. Min Xun
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  3. Yu** Chen
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Yu** Chen conceptualised the manuscript. Yu** Chen and Meichun Wu wrote the manuscript. Meichun Wu and Min Xun designed and prepared the figures and tables. All authors approved the final manuscript.

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Correspondence to Yu** Chen.

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Wu, M., Xun, M. & Chen, Y. Circular RNAs: regulators of vascular smooth muscle cells in cardiovascular diseases. J Mol Med 100, 519–535 (2022). https://doi.org/10.1007/s00109-022-02186-3

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