A tryptophan derivative TD-26 attenuates thrombus formation by inhibiting both PI3K/Akt signaling and binding of fibrinogen to integrin αIIbβ3

Chen, Yahui; Wang, Ying; Xie, Zhouling; Xin, Ming; Li, Zhiyu; Kong, Yi

doi:10.1016/j.bbrc.2015.08.051

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…Downstream experiments have further demonstrated that TD-26 suppresses platelet aggregation by blocking the binding of fibrinogen to integrin and reducing protein kinase B phosphorylation in platelet phosphatidylinositol 3-kinase signaling. 50 Although our results are in line with previous findings, most of the nominally significant metabolites identified by our systemic interrogation failed to pass multiple correction or are attenuated to nonsignificant after adjusting for BMI, making it difficult to draw firm conclusions. There are several potential explanations for this.…”

Section: Discussionsupporting

confidence: 81%

Metabolites Associated With the Risk of Incident Venous Thromboembolism: A Metabolomic Analysis

Jiang

Zeleznik

Lindström

et al. 2018

JAHA

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Background Venous thromboembolism ( VTE ) is a complex thrombotic disorder that constitutes a major source of mortality and morbidity. To improve understanding of the cause of VTE , we conducted a metabolomic analysis in a case‐control study including 240 incident VTE cases and 6963 controls nested within 3 large prospective population‐based cohorts, the Nurses’ Health Study, the Nurses’ Health Study II , and the Health Professionals Follow‐Up Study. Methods and Results For each individual, we measured 211 metabolites and collected detailed information on lifestyle factors. We performed logistic regression and enrichment analysis to identify metabolites and biological categories associated with incident VTE risk, accounting for key confounders, such as age, sex, smoking, alcohol consumption, body mass index, and comorbid diseases (eg, cancers). We performed analyses of all VTEs and separate analyses of pulmonary embolism. Using the basic model controlling for age, sex, and primary disease, we identified 60 nominally significant VTE ‐ or pulmonary embolism–associated metabolites ( P <0.05). These metabolites were enriched for diacylglycerols ( P permutation <0.05). However, after controlling for multiple testing, only 1 metabolite (C5 carnitine; odds ratio, 1.25; 95% confidence interval, 1.10–1.41; P corrected =0.03) remained significantly associated with VTE . After further adjustment for body mass index, no metabolites were significantly associated with disease after accounting for multiple testing, and no metabolite classes were enriched for nominally significant associations. Conclusions Although our findings suggest that circulating metabolites may influence the risk of incident VTE , the associations we observed were confounded by body mass index. Larger studies involving additional individuals and with broader metabolomics coverage are needed to confirm our findings.

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Section: Discussionsupporting

confidence: 81%

Metabolites Associated With the Risk of Incident Venous Thromboembolism: A Metabolomic Analysis

Jiang

Zeleznik

Lindström

et al. 2018

JAHA

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“…PI3K‐Akt signaling pathway regulates platelet activation in thrombus formation [ 58 ]. The expression of the PI3K‐AKt pathway in platelets was enhanced in thrombosis patients, and the inhibition of the signaling pathway may be a potential treatment target for thrombotic diseases [ 59 , 60 ]. MAPK signaling pathway is associated with the pathophysiology of venous thrombosis [ 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Deep sequencing of circulating miRNAs and target mRNAs level in deep venous thrombosis patients

Wang

Chang

Yang

et al. 2023

IET Systems Biology

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Deep venous thrombosis is one of the most common peripheral vascular diseases that lead to major morbidity and mortality. The authors aimed to identify potential differentially expressed miRNAs and target mRNAs, which were helpful in understanding the potential molecule mechanism of deep venous thrombosis. The plasma samples of patients with deep venous thrombosis were obtained for the RNA sequencing. Differentially expressed miRNAs were identified, followed by miRNA‐mRNA target analysis. Enrichment analysis was used to analyze the potential biological function of target mRNAs. GSE19151 and GSE173461 datasets were used for expression validation of mRNAs and miRNAs. 131 target mRNAs of 21 differentially expressed miRNAs were identified. Among which, 8 differentially expressed miRNAs including hsa‐miR‐150‐5p, hsa‐miR‐326, hsa‐miR‐144‐3p, hsa‐miR‐199a‐5p, hsa‐miR‐199b‐5p, hsa‐miR‐125a‐5p, hsa‐let‐7e‐5p and hsa‐miR‐381‐3p and their target mRNAs (PRKCA, SP1, TP53, SLC27A4, PDE1B, EPHB3, IRS1, HIF1A, MTUS1 and ZNF652) were found associated with deep venous thrombosis for the first time. Interestingly, PDE1B and IRS1 had a potential diagnostic value for patients. Additionally, 3 important signaling pathways including p53, PI3K‐Akt and MAPK were identified in the enrichment analysis of target mRNAs (TP53, PRKCA and IRS1). Identified circulating miRNAs and target mRNAs and related signaling pathways may be involved in the process of deep venous thrombosis.

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“…Hence, the platelet aggregation rate is increased in patients with thrombosis, and the expression of platelet-associated active substances is enhanced. In addition, findings have shown that the expression of the PI3K/AKt pathway in platelets was enhanced in thrombosis patients ( 9 ), the PI3K/AKt pathway participates in cell activation, proliferation, apoptosis and other processes ( 10 ), and platelet adhesion, aggregation and release are closely related ( 11 ). Therefore, it could be considered that the activation of the PI3K/AKt signaling pathway is one of the mechanisms of platelet activation.…”

Section: Discussionmentioning

confidence: 99%

“…PI3K can affect the activity of GPIb, GPIIb/IIIa and GPIV ( 19 ), which plays a role in controlling platelet aggregation and release; while AKt platelets could promote the release of the active substance ( 20 ). The study conducted by Chen et al revealed that the tryptophan derivative CD-26 exerts an anti-thrombotic effect by inhibiting the PI3K/Akt pathway in platelets ( 9 ). Furthermore, the study conducted by Hao et al suggested that lutein A may inhibit platelet activation by inhibiting the PI3K/Akt pathway ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Predictive value of platelet aggregation rate in postpartum deep venous thrombosis and its possible mechanism

et al. 2018

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The present study investigated the predictive value of the platelet aggregation rate in postpartum deep venous thrombosis and its possible mechanism. From January 2014 to January 2016, 23 patients with postpartum deep vein thrombosis of lower extremity treated in the Department of Obstetrics of Beijing Chaoyang Hospital were as assigned as the observation group. At the same time, 25 cases with normal recovery were assigned as the control group. Blood samples were collected from all the subjects. The platelet aggregation rate was measured using a platelet aggregation apparatus. Plasma platelet activating factor (PAF) levels were measured by ELISA. The positive rate of platelet P-selectin (CD62p) and lysosomal membrane glycoprotein (CD63) was measured by flow cytometry. PI3K expression and AKt phosphorylation levels were measured by western blot analysis. The ROC curve was used to evaluate the value of the platelet aggregation rate in predicting postpartum deep vein thrombosis of lower extremity. The correlation between the platelet aggregation rate and PAF and PI3K/AKt expression was also analyzed. The cesarean section rate, platelet 5-min maximum aggregation rate, PAF level and the positive rate of CD62p and CD63 were significantly higher in the control than those in the observation group (P<0.05). Furthermore, the platelet aggregation rate was positively correlated with the expression of PAF, CD62p and CD63 (r=0.389, 0.451, and 0.452; all P<0.05). The platelet 5-min maximum aggregation rate for predicting postpartum deep vein thrombosis of lower extremity was reflected by the area under the ROC curve (AUC=0.797, P=0.000). The PI3Kp110β/β-actin and p-AKt/AKt ratio was significantly higher in the observation compared with the control group (P<0.05). In addition, the platelet aggregation rate was positively correlated with the expression of PI3K and phosphorylation level of AKt (r=0.441, 0.430; all P<0.05). The results suggested that platelet aggregation activity is elevated in postpartum deep vein thrombosis patients. It has a certain predictive value for the occurrence of postpartum deep vein thrombosis of lower extremity. Thuss, the PI3K/AKt signaling pathway may be one of the mechanisms of platelet aggregation.

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A tryptophan derivative TD-26 attenuates thrombus formation by inhibiting both PI3K/Akt signaling and binding of fibrinogen to integrin αIIbβ3

Cited by 6 publications

References 35 publications

Metabolites Associated With the Risk of Incident Venous Thromboembolism: A Metabolomic Analysis

Metabolites Associated With the Risk of Incident Venous Thromboembolism: A Metabolomic Analysis

Deep sequencing of circulating miRNAs and target mRNAs level in deep venous thrombosis patients

Predictive value of platelet aggregation rate in postpartum deep venous thrombosis and its possible mechanism

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