Abstract
Xueshuantong capsule (XST) is a patented traditional Chinese medicine used for the prevention and treatment of thrombosis. The molecular mechanism of anti-thrombotic effect of XST was investigated through the cross-talk among the platelets/leukocytes, endothelial cells (ECs), and flow shear stress. The Bioflux 1000 system was used to generate two levels of shear stress conditions: 0.1 and 0.9 Pa. Bioflux Metamorph microscopic imaging system was used to analyze the adhesion cell numbers. Protein expressions were detected by western blotting and flow cytometry. The flow-cytometry results showed that under 0.1 Pa flow, XST decreased ADP induced platelets CD62p surface expression in a concentration-dependent manner. Under 0.9 Pa flow, XST at a concentration of 0.15 g⋅L-1 reduced the platelets activation by 29.5%, and aspirin (ASA) showed no inhibitory effects. XST showed similar efficiency on monocytes adhesion both under 0.1 and 0.9 Pa flow conditions, and the inhibition rate was 30.2 and 28.3%, respectively. Under 0.9 Pa flow, the anti-adhesive effects of XST might be associated with the suppression of VE-cadherin and Cx43 in HUVECs. Blood flow not only acts as a drug transporter, but also exerts its effects to influence the pharmacodynamics of XST. Effects of XST on inhibiting platelets activation and suppressing platelets/leukocytes adhesion to injured ECs are not only concentration-dependent, but also shear stress-dependent. The mechanic forces combined with traditional Chinese medicine may be used as a precise treatment for cardiovascular diseases.
Highlights
The concept of Virchow’s triad regarding the pathogenesis of thrombosis has provided an outline for understanding thrombotic diseases 150 years ago (Wolberg et al, 2012)
The effects of Xueshuantong capsule (XST) at different concentrations on Human umbilical vein endothelial cell (HUVEC) viability were examined by methyl thiazolyl tetrazolium (MTT) assay
Together with the above mentioned evidence, our results revealed that XST showed higher efficacy on thrombosis inhibition under low shear stress condition than ASA did, which is consistent with the studies on the effects of ASA which is known not to have clinically significant efficacy in deep vein thrombosis (DVT)
Summary
The concept of Virchow’s triad regarding the pathogenesis of thrombosis (perturbations in blood, blood vessel, and/or blood flow) has provided an outline for understanding thrombotic diseases 150 years ago (Wolberg et al, 2012). The structure and function of ECs could be influenced by shear stress, which might in turn modulate the expressions of genes and proteins associated with thrombotic diseases (Chatzizisis et al, 2007; Chiu et al, 2009; Chiu and Chien, 2011). In the venous system, altered shear stress may induce the dysfunction of ECs, leading to the development of several chronic venous diseases, such as varicose veins and deep venous thrombosis (Bergan et al, 2006; Chiu and Chien, 2011)
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