Downregulation of interleukin-6 and C-reactive protein underlies a novel inhibitory role of microRNA-136-5p in acute lower extremity deep vein thrombosis

Ou, Minghui; Hao, Shaobo; Chen, Jing; Zhao, Shiqing; Cui, Shichao; Tu, Jie

doi:10.18632/aging.103140

Cited by 10 publications

(14 citation statements)

References 40 publications

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“…EPC-derived EVs significantly promote the resolution of thrombus (11). Overexpression of miR-136-5p could down- regulate the expression of IL-6 and CRP, thereby inhibiting apoptosis of human umbilical vein endothelial cells (15). In an experimental trails in mice, the associated mechanism of DVT was delved by which EPCs-EV-loaded miR-136-5p augmented the dissolution of DVT by suppressing TXNIP.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-136-5p from Endothelial Progenitor Cells-released Extracellular Vesicles Mediates TXNIP to Promote the Dissolution of Deep Venous Thrombosis

Feng

Lei

Zhang

et al. 2022

Shock

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Endothelial progenitor cells-released extracellular vesicles (EPCs-EVs) have previously been reported to promote the dissolution of deep venous thrombosis (DVT) through delivery of microRNA (miR). Given that, this research was projected to search the relative action of EPCs-EVs transferring of miR-136-5p in DVT. Methods: From EPCs transfected with miR-136-5p agomir or antagomir, EVs were extracted and then injected into DVTmice. Meanwhile, based on the treatment with EPCs-EVs loading miR-136-5p antagomir, silenced thioredoxin-interacting protein (TXNIP) lentivirus was injected into DVT mice to perform the rescue experiments. Afterwards, the length and weight of venous thrombosis, EPC apoptosis and inflammatory factors, plasmin, fibrinogen, and thrombin-antithrombin were measured. miR-136-5p and TXNIP expression in DVT mice, and their targeting relationship were evaluated. Results: miR-136-5p expression was suppressed and TXNIP expression was elevated in DVT mice. EPCs-EV reduced the length and weight of venous thrombosis, suppressed cell apoptosis and inflammatory reaction, as well as elevated level of plasmin, and reduced levels of fibrinogen and thrombin-antithrombin in DVT mice. Restored miR-136-5p loaded by EPCs-EV further attenuated DVT but EPCs-EV transfer of depleted miR-136-5p resulted in the opposite consequences. miR-136-5p targeted TXNIP and silenced TXNIP rescued the effect of EPCs-EV transfer of depleted miR-136-5p on DVT. Conclusion: miR-136-5p from EPCs-EV suppresses TXNIP expression to reduce the thrombus size in DVT, offering a promising treatment target for DVT

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Section: Discussionmentioning

confidence: 99%

“…Analysis of miR signatures has found that miR-136-5p is expressed at low levels in plasma of patients with DVT (14). In acute lower extremity DVT, miR-136-5p has been identified as a therapeutic agent to suppress venous thrombus (15). However, the action of EPCs-EV transfer of miR-136-5p in the dissolution of DVT was not discussed.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-136-5p from Endothelial Progenitor Cells-released Extracellular Vesicles Mediates TXNIP to Promote the Dissolution of Deep Venous Thrombosis

Feng

Lei

Zhang

et al. 2022

Shock

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“…However, our study showed that hs-CRP level was not an important predictor of LAAT/SEC. Previous data has shown that reduction in albumin concentration and the plasma CRP level are inflammatory markers that might result in thrombosis [ 21 – 23 ]. These contradictory findings showed that besides inflammation, ALB was another major contributor to the LAAT/SEC.…”

Section: Discussionmentioning

confidence: 99%

A nomogram to predict left atrial appendage thrombus and spontaneous echo contrast in non-valvular atrial fibrillation patients

Sun

Lin

et al. 2022

BMC Cardiovasc Disord

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Background Non-valvular atrial fibrillation (NVAF) significantly increases the risk of stroke. Although there is availability of prediction models, their ability to predict the risk of stroke in NVAF patients remains suboptimal. Therefore, there is need to improve prediction of high-risk individuals, which is critical for efficient management of patients with NVAF. Objective The objective of our paper is to develop a nomogram for predicting the risk of left atrial appendage thrombus (LAAT) and spontaneous echo contrast (SEC), thereby replacing the risk of stroke in NVAF patients. Design This was a retrospective cohort study that analyzed clinical data and echocardiographic indices of 387 patients with NVAF from October 2018 to June 2021. Multivariable logistic regression was used to evaluate independent factors that were used to construct the prediction nomogram. Analysis The discriminative ability and calibration of the nomogram to predict LAAT/SEC were tested using C-statistic and calibration plot. The performance of the nomogram was assessed against the CHA2DS2 score, CHA2DS2-VASc score and ATRIA score using the receiver operating characteristic curve (ROC), decision curve analysis (DCA), integrated discrimination index (IDI) and net reclassification index (NRI). Result Out of the total 387 patients enrolled in this study, 232 had LAAT/SEC. Multivariable analyses demonstrated that N-terminal pro-B-type natriuretic peptide (NT-proBNP), albumin (ALB), LAA ejection fraction (LAAEF) and LAA global peak longitudinal strain (LAA GPLS) were independent predictors of LAAT/SEC. The constructed nomogram had good discriminative (C = 0.886) and calibration (0.876) abilities after bias correction by the C-index. Compared with other models, the decision curve analyses demonstrated that the nomogram had greater net benefits. Besides, the nomogram had significant improvement in predictive performance, sensitivity and reclassification for LAAT/SEC compared with the CHA2DS2 [(c-index: 0.886 vs. 0.576, p < 0.05), (NRI: 0.539, p < 0.05), (IDI: 0.432, p < 0.05)], CHA2DS2-VASc [(c-index: 0.886 vs0.579, p < 0.05), (NRI: 0.513, p < 0.05), (IDI: 0.432, p < 0.05)] or ATRIA [(c-index: 0.886 vs0.583, p < 0.05), (NRI: 0.546, p < 0.05), (IDI: 0.432, p < 0.05)]. Conclusion Taken together, our data demonstrated that the developed nomogram was effective and had potential clinical application in the prediction of LAAT/SEC in patients with NVAF.

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“…At present, the mechanism of vascular endothelial injury in VT mainly involves apoptosis, and the control of vascular endothelial cell apoptosis can reduce thrombosis [ 17 , 18 ]. The process of apoptosis has been shown to have no release of cell contents and therefore no inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

Necroptosis Plays a Crucial Role in Vascular Injury during DVT and Is Enhanced by IL-17B

Chen

Yang

et al. 2022

Journal of Immunology Research

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Background. This study investigated whether vascular endothelial necroptosis is involved in deep vein thrombosis (DVT) and how IL-17B facilitates necroptosis signaling. Methods. The DVT mouse model was induced by ligation of the IVC. The cross-sectional area of thrombus increases and the thrombus occupied the entire venous lumen at 48 h after ligation. Meanwhile, the increased expression of p-RIP3/RIP3 was most pronounced at 48 h after ligation, and the p-MLKL/MLKL peaked at 72 h. Results. Based on Illumina sequencing and KEGG pathway analyses, the activated RIP3/MLKL is associated with increased IL-17B. With thrombus formation, IL-17B was upregulated and enhanced the expression of RIP3 and MLKL in the IVC wall, as well as their phosphorylation levels (all P < 0.05 , the comparison group consisted of the control group, DVT group, DVT/IL-17B group, and DVT/anti-IL-17B group). The p-RIP3/RIP3 and p-MLKL/MLKL ratios were reduced by anti-IL-17B. Similarly, the weight and cross-sectional area of the thrombi were increased by IL-17B and decreased by the IL-17B antibody. IL-17B had a smaller effect on thrombosis in knockout mice compared with WT mice. In vitro, the IL-17B protein expression and the level of RIP3 and MLKL phosphorylation increased high in the OGD cells, accompanied by increased expression of IL-6 and TNF-α. IL-17B enhanced the expression of IL-6 and TNF-α but had little effect on the IL-6 and TNF-α after transfected with siRIP3 or siMLKL. Similarly, the plasma IL-17B, IL-6, and TNF-α were significantly increased after thrombosis in WT mice, and enhanced by IL-17B. But IL-17B did not increase the plasma IL-6 and TNF-α in knockout mice. Conclusions. In conclusion, those results suggest that vascular endothelial necroptosis plays a crucial role in vascular injury and IL-17B could enhance the necroptosis pathway.

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Downregulation of interleukin-6 and C-reactive protein underlies a novel inhibitory role of microRNA-136-5p in acute lower extremity deep vein thrombosis

Cited by 10 publications

References 40 publications

MicroRNA-136-5p from Endothelial Progenitor Cells-released Extracellular Vesicles Mediates TXNIP to Promote the Dissolution of Deep Venous Thrombosis

MicroRNA-136-5p from Endothelial Progenitor Cells-released Extracellular Vesicles Mediates TXNIP to Promote the Dissolution of Deep Venous Thrombosis

A nomogram to predict left atrial appendage thrombus and spontaneous echo contrast in non-valvular atrial fibrillation patients

Necroptosis Plays a Crucial Role in Vascular Injury during DVT and Is Enhanced by IL-17B

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