Differential expression of plasma miRNAs in patients with unprovoked venous thromboembolism and healthy control individuals

Starikova, Irina; Jamaly, Simin; Sorrentino, Antonio; Blöndal, Thórarinn; Latysheva, Nadezhda; Sovershaev, Mikhail A.; Hansen, John‐Bjarne

doi:10.1016/j.thromres.2015.07.005

Cited by 65 publications

(60 citation statements)

References 31 publications

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“…So, alterations of potential miRNA binding sites may have a relevant effect in the expression of the target protein by affecting plasma levels and increasing the risk of thrombosis. Importantly, it has recently been shown that a series of plasma miRNAs are differentially expressed in patients with venous thromboembolism in comparison with healthy controls, strongly suggesting a role for miRNAs in venous thrombosis (Starikova et al, 2015;Wang et al, 2016). Our in vitro results clearly demonstrated that rs4253430 might mechanistically provoke an alteration in the interaction with miRNAs (Fig 2A).…”

Section: Discussionsupporting

confidence: 60%

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Identification of coagulation gene 3′UTR variants that are potentially regulated by microRNAs

et al. 2017

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MicroRNAs have been recognized as critical regulators of gene expression and might affect the risk of venous thrombosis. We aimed to identify 3' untranslated region (UTR) variants in coagulation genes that influence coagulation factor levels and venous thrombosis risk. The 3'UTR of coagulation genes were sequenced in subjects with extremely high or low plasma levels of these factors in two case-control studies. In total, 28 variants were identified. Five single nucleotide polymorphisms (SNPs) were predominantly present in one extreme level group (F2 rs1799963, F8 rs1050705 and F11 rs4253429, rs4253430 and rs1062547). Additional to F2 rs1799963, F8 rs1050705 (in men) and F11 rs4253430 were associated with an increased risk of venous thrombosis albeit confidence intervals were wide. The three F11 SNPs were in high linkage disequilibrium with functional variants rs2289252 and rs2036914. Rs1062547 and rs4253430 were associated with a significant increase of plasma FXI activity in heterozygotes and homozygotes in wild-type controls. In silico prediction revealed that these SNPs might disturb the binding sites of miR-544 and miR-513a-3p. Only miR-544 provoked a significant decrease of the luciferase activity that was not observed with a rs4253430 mutated vector. In conclusion, these results reinforce that microRNAs are candidates to play a role in haemostasis and complex disorders, such as thrombosis.

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Section: Discussionsupporting

confidence: 60%

“…mechanism. Importantly, it has recently been shown that a series of plasma miRNAs are differentially expressed in patients with venous thromboembolism in comparison with healthy controls, strongly suggesting a role for miRNAs in venous thrombosis (Starikova et al, 2015;Wang et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Identification of coagulation gene 3′UTR variants that are potentially regulated by microRNAs

et al. 2017

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“…A previous study identified the diagnostic values of miRNAs in LEDVT. Consistently, miR‐103a‐3p was downregulated in plasmas of venous thromboembolism (VTE) patients as compared with controls . SDF‐1/CXCL12 has been noted to induce thrombosis .…”

Section: Discussionmentioning

confidence: 82%

“…Consistently, miR-103a-3p was downregulated in plasmas of venous thromboembolism (VTE) patients as compared with controls. 23 SDF-1/CXCL12 has been noted to induce thrombosis. 24 Previous evidence has suggested that venous thrombus resolution, an inflammatory process, is dependent on chemokines.…”

Section: Mir-103a-3p Regulates Macrophage Polarization and Venous Tmentioning

confidence: 99%

Overexpressed microRNA‐103a‐3p inhibits acute lower‐extremity deep venous thrombosis via inhibition of CXCL12

et al. 2019

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Studies have shown that microRNAs (miRNAs) participate in almost all pathological and physiological processes including acute lower‐extremity deep venous thrombosis (LEDVT). Here, this study was designed to elucidate the possible function of miR‐103a‐3p in acute LEDVT. Expression of miR‐103a‐3p and chemokine C‐X‐C motif ligand 12 (CXCL12) was initially quantified in plasma collected from 81 LEDVT patients. Then LEDVT mouse models were established by injection with 3% sodium pentobarbital. The interaction between miR‐103a‐3p and CXCL12 was identified by dual‐luciferase reporter gene assay. After gain‐ and loss‐of‐function studies, interleukin‐6 (IL‐6) and IL‐8 and tissue factor (TF) levels, and expression of plasminogen activator inhibitors (PAIs), von Willebrand factor (vWF), thromboxane A2 (TH‐A2), F4/80, IL‐12, Arginase‐1 (Arg‐1) and CD206 were determined using enzyme‐linked immunosorbent assay (ELISA), reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and western blot analysis, respectively. miR‐103a‐3p was downregulated, while CXCL12 was upregulated in patients and mice with LEDVT. miR‐103a‐3p targets CXCL12 and inhibited its expression. Overexpressed miR‐103a‐3p or downregulated CXCL12 decreased expression of IL‐6, IL‐8, TF, PAIs, vWF, TH‐A2, M1 markers (IL‐6 and IL‐12), yet increased expression of M2 markers (Arg‐1 and CD206) in LEDVT mice. Additionally, upregulated miR‐103a‐3p or silencing CXCL12 suppressed thrombosis in LEDVT mice. However, overexpression of CXCL12 reversed the tendency mentioned above. Altogether, miR‐103a‐3p can potentially downregulate CXCL12 expression to disrupt inflammatory response and thrombosis, ultimately preventing the development of LEDVT. Our findings underscore a possible alternative therapeutic strategy to limit LEDVT.

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“…Further study demonstrated that miR‐195 inhibits proliferation, migration, angiogenesis and autophagy of hEPCs under hypoxia by targeting GABA Type A Receptor Associated Protein Like 1 (GABARAPL1),208 and miR‐532 is associated with lipopolysaccharide (LPS)‐stimulated macrophage inflammatory response 209. In plasma assays, one study found that miR‐10b‐5p, miR‐320a, miR‐320b, miR‐424‐5p and miR‐423‐5p are elevated, while miR‐103a‐3p, miR‐191‐5p, miR‐301a‐3p and miR‐199b‐3p are reduced in VTE patients 210. Another study also found miR‐424‐5p is significantly up‐regulated, whereas miR‐136‐5p is down‐regulated in the plasma of DVT patients 211.…”

Section: Clinical Value Of Mirnas As New Biomarkers For Angiogenesis‐mentioning

confidence: 99%

The regulatory role of microRNAs in angiogenesis‐related diseases

Sun

Lei

et al. 2018

J Cellular Molecular Medi

119

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MicroRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression at a post‐transcriptional level via either the degradation or translational repression of a target mRNA. They play an irreplaceable role in angiogenesis by regulating the proliferation, differentiation, apoptosis, migration and tube formation of angiogenesis‐related cells, which are indispensable for multitudinous physiological and pathological processes, especially for the occurrence and development of vascular diseases. Imbalance between the regulation of miRNAs and angiogenesis may cause many diseases such as cancer, cardiovascular disease, aneurysm, Kawasaki disease, aortic dissection, phlebothrombosis and diabetic microvascular complication. Therefore, it is important to explore the essential role of miRNAs in angiogenesis, which might help to uncover new and effective therapeutic strategies for vascular diseases. This review focuses on the interactions between miRNAs and angiogenesis, and miRNA‐based biomarkers in the diagnosis, treatment and prognosis of angiogenesis‐related diseases, providing an update on the understanding of the clinical value of miRNAs in targeting angiogenesis.

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Differential expression of plasma miRNAs in patients with unprovoked venous thromboembolism and healthy control individuals

Cited by 65 publications

References 31 publications

Identification of coagulation gene 3′UTR variants that are potentially regulated by microRNAs

Identification of coagulation gene 3′UTR variants that are potentially regulated by microRNAs

Overexpressed microRNA‐103a‐3p inhibits acute lower‐extremity deep venous thrombosis via inhibition of CXCL12

The regulatory role of microRNAs in angiogenesis‐related diseases

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