Abstract
The formation of a thrombus is closely related to oxidative stress and inflammation. Colchicine is one of the most commonly prescribed medication for gout treatment, with anti-inflammation and antioxidative stress properties. Therefore, we speculated that it is possible for colchicine to treat thrombosis. In this study, we used carrageenan to induce thrombosis in BALB/c mice and fed mice with colchicine, ticagrelor, and their combination, respectively. We found colchicine inhibited carrageenan-induced thrombi in mouse tail, and the inhibition was enhanced by ticagrelor. In vitro, colchicine inhibited thrombin-induced retraction of human platelet clots. Mechanically, colchicine inhibited platelet activation by reducing the expression of platelet receptors, protease-activated receptor 4 (PAR4) and CD36, and inactivating of AKT and ERK1/2 pathways. Furthermore, in human umbilical vein endothelial cells (HUVECs), colchicine showed antioxidative stress effects through increasing protein expression of glutathione peroxidase-1 (GPx-1), and mRNA levels of forkhead box O3 (FOXO3a) and superoxide dismutase 2 (SOD2). In RAW264.7 cells, colchicine reduced LPS-enhanced inflammatory response through attenuating toll-like receptor 4 (TLR4) activation. In addition, colchicine reduced LPS or ox-LDL-induced monocyte adhesion to HUVECs by inhibiting intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) levels. Taken together, our study demonstrates that colchicine exerts antithrombotic function by attenuating platelet activation and inhibiting oxidative stress and inflammation. We also provide a potential new strategy for clinical treatment.
Highlights
A thrombus is a blood clot that forms in the vessels due to coagulation disorder
We found that in human umbilical vein endothelial cells (HUVECs), Buthionine sulfoximine (BSO) reduced glutathione peroxidase-1 (GPx-1) protein and mRNA expression, as well as superoxide dismutase 2 (SOD2) mRNA levels, which were attenuated by the combination treatment of ticagrelor and colchicine (Figures 4(e)–4(g))
Our results showed that colchicine alleviates oxidative stress by increasing the expression of antioxidant enzymes, CAT, GPx-1, and SOD2 in HUVECs and platelets (Figures 4 and 5)
Summary
A thrombus is a blood clot that forms in the vessels due to coagulation disorder. It can cause tissue infarction and other serious complications, such as cerebral embolism and pulmonary embolism, which seriously affect human health. Aspirin, clopidogrel, prasugrel, and ticagrelor have been widely used worldwide for cardiovascular diseases due to their effective antiplatelet aggregation effects [1]. Current clinical studies suggest that ticagrelor combined with aspirin is superior to clopidogrel in the prevention of acute coronary syndrome [2]. These drugs may cause severe side effects including gastrointestinal bleeding, dyspnea, and gout. New or better solutions are still needed for antithrombotic therapy
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