Up regulation of isoleucyl-tRNA synthetase promotes vascular smooth muscle cells dysfunction via p38 MAPK/PI3K signaling pathways

Li, Bowen; Wang, Zhiwei; Chen, Ruoshi; Hong, Junmou; Wu, Qi; Hu, Junxia; Hu, Zhipeng; Zhang, Min

doi:10.1016/j.lfs.2019.03.052

Cited by 11 publications

(7 citation statements)

References 23 publications

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“…The role of PI3K/AKT signaling in the pathophysiology of AAA has been investigated. It has been reported that the activation of PI3K/AKT signaling could attenuate AAA formation by suppressing inflammation and reducing the loss of VSMCs [ 46 , 47 ]. Additionally, some studies have indicated that the gene polymorphism of ERBB3 is closely associated with diabetes [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Plasma Biomarkers for Abdominal Aortic Aneurysm by Protein Array Analysis

Wang

Xie

et al. 2022

Biomolecules

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Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease that is common in the aging population. Currently, there are no approved diagnostic biomarkers or therapeutic drugs for AAA. We aimed to identify novel plasma biomarkers or potential therapeutic targets for AAA using a high-throughput protein array-based method. Proteomics expression profiles were investigated in plasma from AAA patients and healthy controls (HC) using 440-cytokine protein array analysis. Several promising biomarkers were further validated in independent cohorts using enzyme-linked immunosorbent assay (ELISA). Thirty-nine differentially expressed plasma proteins were identified between AAA and HC. Legumain (LGMN) was significantly higher in AAA patients and was validated in another large cohort. Additionally, “AAA without diabetes” (AAN) patients and “AAA complicated with type 2 diabetes mellitus” (AAM) patients had different cytokine expression patterns in their plasma, and nine plasma proteins were differentially expressed among the AAN, AAM, and HC subjects. Delta-like protein 1 (DLL1), receptor tyrosine-protein kinase erbB-3 (ERBB3), and dipeptidyl peptidase 4 (DPPIV) were significantly higher in AAM than in AAN. This study identified several promising plasma biomarkers of AAA. Their role as therapeutic targets for AAA warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Identification of Novel Plasma Biomarkers for Abdominal Aortic Aneurysm by Protein Array Analysis

Wang

Xie

et al. 2022

Biomolecules

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“…Recent studies have found that ARS is also associated with the development and progression of AAA. 87 AAA is a chronic degenerative condition that causes permanent focal dilation of the walls of the abdominal aorta. Several factors are at risk of developing AAA, including age, high blood pressure, smoking, dyslipidemia, and a family history of AAA and other CVDs.…”

Section: Aaamentioning

confidence: 99%

“…Several factors are at risk of developing AAA, including age, high blood pressure, smoking, dyslipidemia, and a family history of AAA and other CVDs. Li et al 87 searched and analyzed the Gene Expression Omnibus (GEO) database and found that IARS mRNA expression was markedly higher in the aortas of AAA patients than in those of patients without AAA. The imbalance of medial aortic injury and repair is an important feature of aortic disease.…”

Section: Aaamentioning

confidence: 99%

The regulatory roles of aminoacyl-tRNA synthetase in cardiovascular disease

Zou

Yang

et al. 2021

Molecular Therapy - Nucleic Acids

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Aminoacyl-tRNA synthetases (ARSs) are widely found in organisms, which can activate amino acids and make them bind to tRNA through ester bond to form the corresponding aminoyl-tRNA. The classic function of ARS is to provide raw materials for protein biosynthesis. Recently, emerging evidence demonstrates that ARSs play critical roles in controlling inflammation, immune responses, and tumorigenesis as well as other important physiological and pathological processes. With the recent development of genome and exon sequencing technology, as well as the discovery of new clinical cases, ARSs have been reported to be closely associated with a variety of cardiovascular diseases (CVDs), particularly angiogenesis and cardiomyopathy. Intriguingly, aminoacylation was newly identified and reported to modify substrate proteins, thereby regulating protein activity and functions. Sensing the availability of intracellular amino acids is closely related to the regulation of a variety of cell physiology. In this review, we summarize the research progress on the mechanism of CVDs caused by abnormal ARS function and introduce the clinical phenotypes and characteristics of CVDs related to ARS dysfunction. We also highlight the potential roles of aminoacylation in CVDs. Finally, we discuss some of the limitations and challenges of present research. The current findings suggest the significant roles of ARSs involved in the progress of CVDs, which present the potential clinical values as novel diagnostic and therapeutic targets in CVD treatment.Although ARS is known for its role in mRNA translation, it is increasingly recognized for its "non-classical" role in transcriptional regulation, intron splicing, immune function, angiogenesis, apoptosis, and

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“…It was suggested that In terms of mechanism, previous studies have suggested that MAPK pathway, consist of JNK (c-Jun NH2-terminal kinase) MAPK, P38 MAPK, and ERK (extracellular signal-regulated kinase) MAPK, participates in ROS production and the development of AAA. [31][32][33][34] First, we surveyed several key mediators in MAPK pathways, including phosphorylated JNK, phosphorylated P38, and phosphorylated ERK. We observed a profound activation of P38 MAPK pathway instead of JNK MAPK pathway or ERK MAPK pathway in Drd4 −/− aortas, evidenced by marked enhancement of P38 phosphorylation but not total P38 (Figure 5B, lower, Figure S3A).…”

Section: Depletion Of Drd4 Induced More Ros Via P38 Mapk/nox4 Axis In...mentioning

confidence: 99%

DRD4 (Dopamine D4 Receptor) Mitigate Abdominal Aortic Aneurysm via Decreasing P38 MAPK (mitogen-activated protein kinase)/NOX4 (NADPH Oxidase 4) Axis–Associated Oxidative Stress

et al. 2021

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Oxidative stress plays a vital role in the development of abdominal aortic aneurysm (AAA). DRD4 (dopamine D4 receptor) is involved in oxidative stress. Here, we reasoned that DRD4 may mitigate AAA by its antioxidative effect. Currently, in vivo, DRD4 expression was reduced in AAA patients and experimental models determined by quantitative polymerase chain reaction and Western blot. Reactive oxygen species (ROS) was increased in elastase perfused aorta from Drd4 −/− mice compared with elastase perfused wild-type ( WT ) aorta determined by dihydroethidium staining and malondialdehyde, accompanying with more apoptotic vascular smooth muscle cells, inflammatory infiltration, and ECM (extracellular matrix) degradation determined by terminal deoxynucleotidyl transferase-mediated nick end labeling assay, immunohistochemistry, Van Gieson staining, and zymography, respectively. However, pharmacological activation of DRD4 reduced the ROS production and mitigated pathological characteristics of AAA. In vitro, activated DRD4 alleviated ROS production and apoptosis determined by 2,7-dichlorodihydrofluorescein diacetate, dihydroethidium, malondialdehyde, and flow cytometry, whereas DRD4 deficiency or inhibited DRD4 exerted the opposite effect in vascular smooth muscle cells. In terms of mechanism, in vivo, DRD4 deficiency upregulated NOX4 (NADPH oxidase 4) expression instead of other subunits, meanwhile, phosphorylated P38 mitogen-activated protein kinase was also augmented instead of other mitogen-activated protein kinase pathways. In vitro, pharmacological activation of DRD4 downregulated phosphorylated P38 and NOX4 in vascular smooth muscle cells, vice versa. Interestingly, DRD4 mediated the expression of NOX4 through a P38 mitogen-activated protein kinase pathway–dependent manner, which regulated ROS production. DRD4 mitigated AAA progression by downregulating P38 mitogen-activated protein kinase/NOX4 axis mediated ROS production in vascular smooth muscle cells. Therefore, DRD4 may serve as a novel therapeutic target for AAA treatment.

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Up regulation of isoleucyl-tRNA synthetase promotes vascular smooth muscle cells dysfunction via p38 MAPK/PI3K signaling pathways

Cited by 11 publications

References 23 publications

Identification of Novel Plasma Biomarkers for Abdominal Aortic Aneurysm by Protein Array Analysis

Identification of Novel Plasma Biomarkers for Abdominal Aortic Aneurysm by Protein Array Analysis

The regulatory roles of aminoacyl-tRNA synthetase in cardiovascular disease

DRD4 (Dopamine D4 Receptor) Mitigate Abdominal Aortic Aneurysm via Decreasing P38 MAPK (mitogen-activated protein kinase)/NOX4 (NADPH Oxidase 4) Axis–Associated Oxidative Stress

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