Association between Exosomal miRNAs and Coronary Artery Disease by Next-Generation Sequencing

Chang, Sheng‐Nan; Chen, Jien-Jiun; Wu, Jo‐Hsuan; Chung, Yao-Te; Chen, Jin-Wun; Chiu, Chu-Hsuan; Liu, Chia‐Ju; Liu, Meng-Tsun; Chang, Yi‐Cheng; Li, Chin; Lin, Jou‐Wei; Hwang, Juey‐Jen; Lien, Wen-Pin

doi:10.3390/cells11010098

Cited by 11 publications

(5 citation statements)

References 23 publications

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“…containing circ_0006896 were increased in patients with unstable carotid atherosclerosis (Wen et al, 2021;Zhang et al, 2020). In contrast, and lncRNA SOCS2-AS1 from the circulating EVs were found to be decreased (Chang et al, 2021;de Gonzalo-Calvo et al, 2016;Liang et al, 2020). This demonstrates the great potential of circulating EV-carried ncRNAs as biomarkers in atherosclerotic CVD.…”

Section: Figure 1 Biogenesis and Characterization Of The Different Ex...mentioning

confidence: 88%

“…The expression levels of several ncRNAs have been found to be increased in circulating EVs from patients with atherosclerosis and coronary artery disease. These include miR‐30e, miR‐92a, miR‐200a, miR‐382, miR‐432, miR‐3613, lncRNA HIF1A‐AS1 and circ_0005540 (Chang et al., 2021; Liu et al., 2019; Wang et al., 2017; Wu et al., 2020; Zhang et al., 2017). Serum‐derived EVs and their miR‐32, miR‐149 and miR‐942 were increased in patients with stable coronary artery disease, while serum‐derived EVs containing circ_0006896 were increased in patients with unstable carotid atherosclerosis (Wen et al., 2021; Zhang et al., 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Serum‐derived EVs and their miR‐32, miR‐149 and miR‐942 were increased in patients with stable coronary artery disease, while serum‐derived EVs containing circ_0006896 were increased in patients with unstable carotid atherosclerosis (Wen et al., 2021; Zhang et al., 2020). In contrast, miR‐125a, miR‐151a, miR‐185, miR‐222, miR‐328 and lncRNA SOCS2‐AS1 from the circulating EVs were found to be decreased (Chang et al., 2021; de Gonzalo‐Calvo et al., 2016; Liang et al., 2020). This demonstrates the great potential of circulating EV‐carried ncRNAs as biomarkers in atherosclerotic CVD.…”

Section: Introductionmentioning

confidence: 99%

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Extracellular vesicles and their non‐coding RNA cargos: Emerging players in cardiovascular disease

Collado

Gan

Tengbom

et al. 2022

The Journal of Physiology

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Extracellular vesicles (EVs), including exosomes, microvesicles and apoptotic bodies, have recently received attention as essential mechanisms for cell‐to‐cell communication in cardiovascular disease. EVs can be released from different types of cells, including endothelial cells, smooth muscle cells, cardiac cells, fibroblasts, platelets, adipocytes, immune cells and stem cells. Non‐coding (nc)RNAs as EV cargos have recently been investigated in the cardiovascular system. Up‐ or downregulated ncRNAs in EVs have been shown to play a crucial role in various cardiovascular diseases. Communication via EV‐derived ncRNAs can occur between cells of the same type and between different types of cells involved in the pathophysiology of cardiovascular disease. In the present review, we highlight the important aspects of diverse cell‐derived EVs and their ncRNA cargos as disease mediators and potential therapeutic targets in atherosclerosis, coronary artery disease, ischaemic heart disease and cardiac fibrosis. In addition, we summarize the potential of EV‐derived ncRNAs in the treatment of cardiovascular disease. Finally, we discuss the different methods for EV isolation and characterization. A better understanding of the specific role of EVs and their ncRNA cargos in the regulation of cardiovascular (dys)function will be of importance for the development of diagnostic and therapeutic tools for cardiovascular disease. image

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Section: Figure 1 Biogenesis and Characterization Of The Different Ex...mentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular vesicles and their non‐coding RNA cargos: Emerging players in cardiovascular disease

Collado

Gan

Tengbom

et al. 2022

The Journal of Physiology

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“…This indicates that TGF-β could play a direct role in -3613-3p expression when acquiring a senescent MSC phenotype. Previous studies have directly linked increased expression of exosome -3613-3p to activating invasive cellular and mechanical properties [ 33 , 51 ]. Therefore, reduced expression of 3613-3p with SB505 treatment could indicate that these MSCs possess limited activation potential to acquire CAF-like phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Senescence-associated exosomes transfer miRNA-induced fibrosis to neighboring cells

Lee

Ghosh

Koh

et al. 2023

Aging

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Radiation-induced fibrosis is a common side effect of radiotherapy, which is the most common treatment for cancer. However, radiation also causes p53-mediated cell cycle arrest, prolonged expression of p21, and the development of senescence in normal cells that reside in irradiated tissues. Bone marrow-derived mesenchymal stem cells (MSCs) accumulate in primary tumor sites because of their natural tropism for inflammatory and fibrotic tissues. MSCs are extremely sensitive to low doses of ionizing radiation and acquire senescence as a result of bystander radiation effects. Senescent cells remain metabolically active but develop a potent senescence-associated secretory phenotype (SASP) that correlates to hyperactive secretion of cytokines, pro-fibrotic growth factors, and exosomes (EXOs). Integrative pathway analysis highlighted that radiationinduced senescence significantly enriched cell-cycle, extracellular matrix, transforming growth factor-β (TGF-β) signaling, and vesicle-mediated transport genes in MSCs. EXOs are cell-secreted nanovesicles (a subclass of small extracellular vesicles) that contain biomaterials-proteins, RNAs, microRNAs (miRNAs)-that are critical in cell-cell communication. miRNA content analysis of secreted EXOs further revealed that radiation-induced senescence uniquely altered miRNA profiles. In fact, several of the standout miRNAs directly targeted TGF-β or downstream genes. To examine bystander effects of radiation-induced senescence, we further treated normal MSCs with senescence-associated EXOs (SA-EXOs). These modulated genes related to TGF-β pathway and elevated both alpha smooth muscle actin (protein increased in senescent, activated cells) and Ki-67 (proliferative marker) expression in SA-EXO treated MSCs compared to untreated MSCs. We revealed SA-EXOs possess unique miRNA content that influence myofibroblast phenotypes via TGF-β pathway activation. This highlights that SA-EXOs are potent SASP factors that play a large role in cancer-related fibrosis.

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“…miRNAs can integrate their effects to accomplish a nuanced result, no matter whether the result is beneficial or detrimental, by controlling the expression of many targets and gene networks. Chang et al identified eight exosomal miRNA profiles from exosomes extracted from coronary blood samples as potential biomarkers and predictors of stable CA [ 42 ]. Some miRNAs, such as miR-139-5p [ 43 ], miR-145 [ 44 ], miR-100 [ 45 ], miR-194-5p [ 46 ], miR-199a-3p [ 46 ] and miR-199b-3p [ 46 ], which may regulate CA, have been identified.…”

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Expressed Genes and Prediction of Expression Regulation Networks in Dysfunctional Endothelium

Cheng

Zeng

Zhao

et al. 2022

Genes

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The detection of early coronary atherosclerosis (ECA) is still a challenge and the mechanism of endothelial dysfunction remains unclear. In the present study, we aimed to identify differentially expressed genes (DEGs) and the regulatory network of miRNAs as well as TFs in dysfunctional endothelium to elucidate the possible pathogenesis of ECA and find new potential markers. The GSE132651 data set of the GEO database was used for the bioinformatic analysis. Principal component analysis (PCA), the identification of DEGs, correlation analysis between significant DEGs, the prediction of regulatory networks of miRNA and transcription factors (TFs), the validation of the selected significant DEGs, and the receiver operating characteristic (ROC) curve analysis as well as area under the curve (AUC) values were performed. We identified ten genes with significantly upregulated signatures and thirteen genes with significantly downregulated signals. Following this, we found twenty-two miRNAs regulating two or more DEGs based on the miRNA–target gene regulatory network. TFs with targets ≥ 10 were E2F1, RBPJ, SSX3, MMS19, POU3F3, HOXB5, and KLF4. Finally, three significant DEGs (TOX, RasGRP3, TSPAN13) were selected to perform validation experiments. Our study identified TOX, RasGRP3, and TSPAN13 in dysfunctional endothelium and provided potential biomarkers as well as new insights into the possible molecular mechanisms of ECA.

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Association between Exosomal miRNAs and Coronary Artery Disease by Next-Generation Sequencing

Cited by 11 publications

References 23 publications

Extracellular vesicles and their non‐coding RNA cargos: Emerging players in cardiovascular disease

Extracellular vesicles and their non‐coding RNA cargos: Emerging players in cardiovascular disease

Senescence-associated exosomes transfer miRNA-induced fibrosis to neighboring cells

Identification of Differentially Expressed Genes and Prediction of Expression Regulation Networks in Dysfunctional Endothelium

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