IQCA-TAVV: To explore the effect of P-selectin, GPIIb/IIIa, IL-2, IL-6 and IL-8 on deep venous thrombosis

Abstract

Deep vein thrombosis (DVT) associates with considerable morbidity, functional disability and mortality. Due to the lack of suitable inhibitor the correlation of various factors in DVT onset remains unknown. In this context we analyzed the structure of anti-platelet aggregation agent, P-selectin down-regulator, GPIIb/ IIIa down-regulator and anti-inflammatory agent, thereby designed N-(3S-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-Thr-Ala-Arg-Gly-Asp(Val)-Val (IQCA-TAVV) as an inhibitor of DVT to receive evaluations. The docking predicted that IQCA-TAVV can target P-selectin and GPIIb/IIIa. The UV showed that IQCA-TAVV can act on P-selectin and GPIIb/IIIa. ELISA indicated that IQCA-TAVV concentration dependently inhibited activated platelets to express P-selectin and GPIIb/IIIa, and the minimal effective concentration was 1 nM. IC 50 of IQCA-TAVV against platelet aggregation induced by arachidonic acid, adenosine diphosphate and platelet activating factor fell within a range of 0.13 nM to 0.30 nM. In vivo IQCA-TAVV dose-dependently inhibited venous thrombosis and the minimal effective dose was 1 nmol/kg. On ear edema model the anti-inflammation activity of 10 nmol/kg IQCA-TAVV equaled that of 1.1mmol/kg aspirin. The concentration of IL-2, IL-6 and IL-8 in the serum of the ear edema mice were also significantly decreased by 10 nmol/kg IQCA-TAVV. Even at 1 μmol/kg of dose IQCA-TAVV still did not injure the kidney, the liver, and the nerves of healthy mice. Thereby IQCA-TAVV depicts a relationship of three levels (inhibiting platelet activation, targeting externalized membrane receptor, decreasing serum inflammatory factor) for the down-regulation of P-selectin, GPIIb/IIIa, IL-2, IL-6 and IL-8 in DVT.

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

“…Subsequently, we found that overexpressed miR‐103a‐3p downregulated CXCL12 expression to reduce inflammatory response and thrombosis, which was verified by decreased IL‐6, IL‐8, and TF, PAIs, vWF, and TH‐A2 expression in response to miR‐103a‐3p agomir injection in mice. Previous evidence has demonstrated that downregulation of certain inflammatory cytokines, including IL‐6 and IL‐8, is closely associated with alleviated inflammation in DVT . It has been reported that miR‐146a/b downregulates the senescence through the inhibition of the secretion of inflammatory cytokines IL‐6 and IL‐8 .…”

“…Previous evidence has demonstrated that downregulation of certain inflammatory cytokines, including IL-6 and IL-8, is closely associated with alleviated inflammation in DVT. 32 It has been reported that miR-146a/b downregulates the senescence through the inhibition of the secretion of inflammatory cytokines IL-6 and IL-8. 33 The mRNA level of TF in leukocytes is higher in patients with DVT than that in healthy individuals.…”

Predictive value of lymphocyte to monocyte ratio and monocyte to high-density lipoprotein ratio for acute deep vein thrombosis after total joint arthroplasty: a retrospective study

“…Moreover, excessive proinflammatory and prooxidant cytokines also do harm to blood vessel walls, making the condition worse [ 8 ]. Considering the crucial role inflammation plays in initiation and progression of thrombosis, various inflammatory biomarkers including CRP (C-reactive protein) and IL-6 (interleukin-6) have been reported to be valuable to predict DVT [ 6 , 8 , 9 ].…”

Platelet Activation and Cytokine Release of Interleukin-8 and Interferon-Gamma-Induced Protein 10 after ChAdOx1 nCoV-19 Coronavirus Vaccine Injection

“…The activation of platelets and inflammatory factors is closely related to vascular endothelial function injury in patients with hypertension [ 40 ]. According to a previous study on deep vein thrombosis, platelet activation is involved in endothelial cells and serum inflammatory factors, with the regulation of p -selectin, GPIIb/IIIa, IL-2, IL-6, and IL-8 [ 41 ]. According to a VITT study by Ostrowski et al [ 14 ], specific components of the AZ adenovirus vector may serve as initial triggers of inflammation, platelet activation, and thrombin generation.…”