Abstract
Lower extremity deep vein thrombosis (LEDVT), a common peripheral vascular disease caused by a blood clot in a deep vein is usually accompanied by swelling of the lower limbs. MicroRNAs (miRs) have been reported to play roles in LEDVT. We aimed to investigate the effect of miR-495 on LEDVT via toll-like receptor 4 (TLR4) signaling pathway through interleukin 1 receptor type 1 (IL1R1). LEDVT mouse model was established, and the femoral vein (FV) tissues were collected to detect expressions of miR-495, IL1R1, and TLR4 signaling-related genes. The expressions of both CD31 and CD34 (markers for endothelial progenitor cells) in the FV endothelial cells as well as the proportion of CD31+/CD34+ cells in peripheral blood were measured in order to evaluate thrombosis. The effect of miR-495 on cell viability, cell cycle, and apoptosis was analyzed. IL1R1 was confirmed as the target gene of miR-495. Besides, inhibiting the miR-495 expression could increase IL1R1 expression along with activating the TLR4 signaling pathway. The total number of the leukocytes along with the ratio of weight to length of thrombus in the FV tissue showed an increase. The overexpression of miR-495 could promote FV endothelial cell viability. By injecting agomiR-495 and antagomiR-495 in vivo, the number of leukocytes in the FV tissues and the ratio of weight to length of thrombus were significantly decreased in the mice injected with the overexpressed miR-495, and the IL1R1/TLR4 signaling pathway was inhibited. Collectively, overexpressed miR-495 directly promotes proliferation while simultaneously inhibiting apoptosis of FV endothelial cells, alleviating FV thrombosis by inhibiting IL1R1 via suppression of TLR4 signaling pathway.
Highlights
Thrombosis, usually present in the form of a blood clot, occurs in any part of the venous system, but frequently in the legs [1,2]
Partial vascular endothelial cell (VEC) were exfoliated with the structure of vascular smooth muscle in disorder, while plenty of inflammatory cells on vascular wall and tissue space were involved with focal infiltration; the vascular wall was further thinning and the thrombi had been spread to most parts of lumen
In comparison with the normal group, the ratio of weight to length of thrombi as well as the number of leukocytes was increased in mice of the model group (P
Summary
Thrombosis, usually present in the form of a blood clot, occurs in any part of the venous system, but frequently in the legs [1,2]. Lower extremity deep vein thrombosis (LEDVT) is both a common and serious peripheral vascular disease, triggering a chief morbidity along with mortality for limb loss, paradoxical embolization, pulmonary embolism, or post-thrombotic syndrome [3]. Tenderness, edema, and swelling of the lower extremity are the most commonly found symptoms amongst LEDVT patients; over 30% of these cases present no signs or symptoms until an association is involved above the knee [5]. The Society of Interventional Radiology and the Society for Vascular Surgery has published quality improvement guidelines for the treatment of LEDVT and a relatively large amount of studies have reported a series of treatment options, no effective pharmacological methods that prevent thrombus-related damage to the vein wall in order to diminish the risk have been discovered [6]
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