FoxO1 regulates asymmetric dimethylarginine via downregulation of dimethylaminohydrolase 1 in human endothelial cells and subjects with atherosclerosis

Menghini, Rossella; Casagrande, Viviana; Cardellini, Marina; Ballanti, Marta; Davato, Francesca; Cardolini, Iris; Stoehr, Robert; Fabrizi, Marta; Morelli, Moreno; Anemona, Lucia; Bernges, Isabel; Schwedhelm, Edzard; Ippoliti, Arnaldo; Mauriello, Alessandro; Böger, Rainer H.; Federici, Massimo

doi:10.1016/j.atherosclerosis.2015.07.026

Cited by 25 publications

(17 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KEGG analysis showed that FOXO1 was enriched into pathways in cancer, AMPK signaling pathway, FOXO signaling pathway, prostate cancer and insulin resistance, etc., all of which remarkably overlapped signaling pathways of circ_0003204 (Additional file 1: Figure S3D). in addition, it was found that FOXO pathway was involved in endothelial protection against atherosclerosis [28], in which TGFβR2, a predictive target of miR-370 by combination of Targetscan, miRDB and miRanda, was involved as well [29] (Additional file 1: Figure S5). Interestingly, TGFβR2 was found to participate in TGFβ signaling pathway [30] with which signaling pathways of circ_0003204 also shared (Additional file 1: Figure S2D).…”

Section: Resultsmentioning

confidence: 99%

RETRACTED ARTICLE: Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFβR2/phosph-SMAD3 axis

Zhang¹,

Song²,

Yuan³

et al. 2020

J Biomed Sci

108

View full text Add to dashboard Cite

Background: Circular RNAs (circRNAs) represent a class of non-coding RNAs (ncRNAs) which are widely expressed in mammals and tissue-specific, of which some could act as critical regulators in the atherogenesis of cerebrovascular disease. However, the underlying mechanisms by which circRNA regulates the ectopic phenotype of endothelial cells (ECs) in atherosclerosis remain largely elusive. Methods: CCK-8, transwell, wound healing and Matrigel assays were used to assess cell viability, migration and tube formation. QRT-qPCR and Immunoblotting were used to examine targeted gene expression in different groups. The binding sites of miR-370-3p (miR-370) with TGFβR2 or hsa_circ_0003204 (circ_0003204) were predicted using a series of bioinformatic tools, and validated using dual luciferase assay and RNA immunoprecipitation (RIP) assay. The localization of circ_0003204 and miR-370 in ECs were investigated by fluorescence in situ hybridization (FISH). Gene function and pathways were enriched through Metascape and gene set enrichment analysis (GSEA). The association of circ_0003204 and miR-370 in extracellular vesicles (EVs) with clinical characteristics of patients were investigated using multiple statistical analysis. Results: Circ_0003204, mainly located in the cytoplasm of human aorta endothelial cells (HAECs), was upregulated in the ox-LDL-induced HAECs. Functionally, the ectopic expression of circ_0003204 inhibited proliferation, migration and tube formation of HAECs exposed to ox-LDL. Mechanically, circ_0003204 could promote protein expression of TGFβR2 and its downstream phosph-SMAD3 through sponging miR-370, and miR-370 targeted the 3′ untranslated region (UTR) of TGFβR2. Furthermore, the expression of circ_0003204 in plasma EVs was upregulated in the patients with cerebral atherosclerosis, and represented a potential biomarker for diangnosis and prognosis of cerebrovascular atherogenesis. Conclusions: Circ_0003204 could act as a novel stimulator for ectopic endothelial inactivation in atherosclerosis and a potential biomarker for cerebral atherosclerosis.

show abstract

Section: Resultsmentioning

confidence: 99%

RETRACTED ARTICLE: Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFβR2/phosph-SMAD3 axis

Zhang¹,

Song²,

Yuan³

et al. 2020

J Biomed Sci

108

View full text Add to dashboard Cite

show abstract

“…Previous research also indicates that FOXO1 can inhibit the synthesis of endothelial nitric oxide synthase and promote the production of inducible NOS, leading to peroxynitrite deposition and endothelial dysfunction 45 , 46 . Additionally, FOXO1 expression in the endothelial cells of unstable plaques was shown to be significantly increased, promoting the dysfunction of vascular endothelial cells in the plaques and reducing the stability of atherosclerosis plaques, which caused plaque rupture, leading to acute thrombotic events, including acute coronary syndrome 47 . These data indicate that FOXO1 plays an important role in the occurrence, development, and plaque instability of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

METTL14 aggravates endothelial inflammation and atherosclerosis by increasing FOXO1 N6-methyladeosine modifications

et al. 2020

View full text Add to dashboard Cite

Aims: The N6-methyladenosine (m 6 A) modification plays an important role in various biological processes, but its role in atherosclerosis remains unknown. The aim of this study was to investigate the role and mechanism of m 6 A modification in endothelial cell inflammation and its influence on atherosclerosis development. Methods: We constructed a stable TNF-α-induced endothelial cell inflammation model and assessed the changes in the expression of m 6 A modification-related proteins to identify the major factors involved in this process. The m 6 A-modified mRNAs were identified by methylated RNA immunoprecipitation (RIP) sequencing and forkhead box O1 (FOXO1) was selected as a potential target. Through cytological experiments, we verified whether methyltransferase-like 14 (METTL14) regulates FOXO1 expression by regulating m 6 A-dependent mRNA and protein interaction. The effect of METTL14 on atherosclerosis development in vivo was verified using METTL14 knockout mice. Results: These findings confirmed that METTL14 plays major roles in TNF-α-induced endothelial cell inflammation. During endothelial inflammation, m 6 A modification of FOXO1, an important transcription factor, was remarkably increased. Moreover, METTL14 knockdown significantly decreased TNF-α-induced FOXO1 expression. RIP assay confirmed that METTL14 directly binds to FOXO1 mRNA, increases its m 6 A modification, and enhances its translation through subsequent YTH N6-methyladenosine RNA binding protein 1 recognition. Furthermore, METTL14 was shown to interact with FOXO1 and act directly on the promoter regions of VCAM-1 and ICAM-1 to promote their transcription, thus mediating endothelial cell inflammatory response. In vivo experiments showed that METTL14 gene knockout significantly reduced the development of atherosclerotic plaques. Conclusion: METTL14 promotes FOXO1 expression by enhancing its m 6 A modification and inducing endothelial cell inflammatory response as well as atherosclerotic plaque formation. Decreased expression of METTL14 can inhibit endothelial inflammation and atherosclerosis development. Therefore, METTL14 may serve as a potential target for the clinical treatment of atherosclerosis.

show abstract

“…Endothelial cells play central roles in the functions of the cardiovascular system 83. Endothelial cell dysfunction causes the accumulation of lipids, inflammatory cells, and coagulation materials as well as vascular smooth muscle cell (VSMC) proliferation, thus promoting atherosclerotic plaque formation 84. Numerous clinical studies have shown that vascular endothelial cell dysfunction is the initiator of and key link to ensuing atherosclerosis 84.…”

Section: Physiopathological Roles Of Stat3 In Atherosclerosismentioning

confidence: 99%

“…Endothelial cell dysfunction causes the accumulation of lipids, inflammatory cells, and coagulation materials as well as vascular smooth muscle cell (VSMC) proliferation, thus promoting atherosclerotic plaque formation 84. Numerous clinical studies have shown that vascular endothelial cell dysfunction is the initiator of and key link to ensuing atherosclerosis 84. Furthermore, endothelial cell dysfunction is closely related to injuries induced by various types of hazards (smoking, hyperlipidemia, oxygen free radicals, etc.)…”

Section: Physiopathological Roles Of Stat3 In Atherosclerosismentioning

confidence: 99%

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis

et al. 2019

View full text Add to dashboard Cite

Atherosclerosis is the main pathological basis of ischemic cardiovascular and cerebrovascular diseases and has attracted more attention in recent years. Multiple studies have demonstrated that the signal transducer and activator of transcription 3 (STAT3) plays essential roles in the process of atherosclerosis. Moreover, aberrant STAT3 activation has been shown to contribute to the occurrence and development of atherosclerosis. Therefore, the study of STAT3 inhibitors has gradually become a focal research topic. In this review, we describe the crucial roles of STAT3 in endothelial cell dysfunction, macrophage polarization, inflammation, and immunity during atherosclerosis. STAT3 in mitochondria is mentioned as well. Then, we present a summary and classification of STAT3 inhibitors, which could offer potential treatment strategies for atherosclerosis. Furthermore, we enumerate some of the problems that have interfered with the development of mature therapies utilizing STAT3 inhibitors to treat atherosclerosis. Finally, we propose ideas that may help to solve these problems to some extent. Collectively, this review may be useful for developing future STAT3 inhibitor therapies for atherosclerosis.

show abstract

FoxO1 regulates asymmetric dimethylarginine via downregulation of dimethylaminohydrolase 1 in human endothelial cells and subjects with atherosclerosis

Cited by 25 publications

References 39 publications

RETRACTED ARTICLE: Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFβR2/phosph-SMAD3 axis

RETRACTED ARTICLE: Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFβR2/phosph-SMAD3 axis

METTL14 aggravates endothelial inflammation and atherosclerosis by increasing FOXO1 N6-methyladeosine modifications

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis

Contact Info

Product

Resources

About