Advances in microRNA regulation of deep vein thrombosis through venous vascular endothelial cells (Review).

Deep vein thrombosis (DVT) is a prevalent clinical venous thrombotic condition that often manifests independently or in conjunction with other ailments. Thrombi have the propensity to dislodge into the circulatory system, giving rise to complications such as pulmonary embolism, thereby posing a significant risk to the patient. Virchow proposed that blood stagnation, alterations in the vessel wall and hypercoagulation are primary factors contributing to the development of venous thrombosis. Vascular endothelial cells (VECs) constitute the initial barrier to the vascular wall and are a focal point of ongoing research. These cells exert diverse stimulatory effects on the bloodstream and secrete various regulatory factors that uphold the dynamic equilibrium between the coagulation and anticoagulation processes. MicroRNAs (miRNAs) represent a class of non­coding RNAs present in eukaryotes, characterized by significant genetic and evolutionary conservation and displaying high spatiotemporal expression specificity. Typically ranging from 20 to 25 bases in length, miRNAs can influence downstream gene transcription through RNA interference or by binding to specific mRNA sites. Consequently, advancements in understanding the molecular mechanisms of miRNAs, including their functionalities, involve modulation of vascular­associated processes such as cell proliferation, differentiation, secretion of inflammatory factors, migration, apoptosis and vascular remodeling regeneration. miRNAs play a substantial role in DVT formation via venous VECs. In the present review, the distinct functions of various miRNAs in endothelial cells are outlined and recent progress in comprehending their role in the pathogenesis and clinical application of DVT is elucidated.

miR-328-3p targets TLR2 to ameliorate oxygen-glucose deprivation injury and neutrophil extracellular trap formation in HUVECs via inhibition of the NF-κB signaling pathway.

BACKGROUND: Endothelial cell injury is one of the important pathogenic mechanisms in thrombotic diseases, and also neutrophils are involved. MicroRNAs (miRNAs) have been demonstrated to act as essential players in endothelial cell injury, but the potential molecular processes are unknown. In this study, we used cellular tests to ascertain the protective effect of miR-328-3p on human umbilical vein endothelial cells (HUVECs) treated with oxygen-glucose deprivation (OGD). METHODS: In our study, an OGD-induced HUVECs model was established, and we constructed lentiviral vectors to establish stable HUVECs cell lines. miR-328-3p and Toll-like receptor 2 (TLR2) interacted, as demonstrated by the dual luciferase reporter assay. We used the CCK8, LDH release, and EdU assays to evaluate the proliferative capacity of each group of cells. To investigate the expression of TLR2, p-P65 NF-κB, P65 NF-κB, NLRP3, IL-1ß, and IL-18, we employed Western blot and ELISA. Following OGD, each group's cell supernatants were gathered and co-cultured with neutrophils. An immunofluorescence assay and Transwell assay have been performed to determine whether miR-328-3p/TLR2 interferes with neutrophil migration and neutrophil extracellular traps (NETs) formation. RESULTS: In OGD-treated HUVECs, the expression of miR-328-3p is downregulated. miR-328-3p directly targets TLR2, inhibits the NF-κB signaling pathway, and reverses the proliferative capacity of OGD-treated HUVECs, while inhibiting neutrophil migration and neutrophil extracellular trap formation. CONCLUSIONS: miR-328-3p inhibits the NF-κB signaling pathway in OGD-treated HUVECs while inhibiting neutrophil migration and NETs formation, and ameliorating endothelial cell injury, which provides new ideas for the pathogenesis of thrombotic diseases.

Research progress of NF-κB signaling pathway and thrombosis.

Venous thromboembolism is a very common and costly health problem. Deep-vein thrombosis (DVT) can cause permanent damage to the venous system and lead to swelling, ulceration, gangrene, and other symptoms in the affected limb. In addition, more than half of the embolus of pulmonary embolism comes from venous thrombosis, which is the most serious cause of death, second only to ischemic heart disease and stroke patients. It can be seen that deep-vein thrombosis has become a serious disease affecting human health. In recent years, with the deepening of research, inflammatory response is considered to be an important pathway to trigger venous thromboembolism, in which the transcription factor NF-κB is the central medium of inflammation, and the NF-κB signaling pathway can regulate the pro-inflammatory and coagulation response. Thus, to explore the mechanism and make use of it may provide new solutions for the prevention and treatment of thrombosis.

Neutrophil extracellular traps mediate deep vein thrombosis: from mechanism to therapy.

Deep venous thrombosis (DVT) is a part of venous thromboembolism (VTE) that clinically manifests as swelling and pain in the lower limbs. The most serious clinical complication of DVT is pulmonary embolism (PE), which has a high mortality rate. To date, its underlying mechanisms are not fully understood, and patients usually present with clinical symptoms only after the formation of the thrombus. Thus, it is essential to understand the underlying mechanisms of deep vein thrombosis for an early diagnosis and treatment of DVT. In recent years, many studies have concluded that Neutrophil Extracellular Traps (NETs) are closely associated with DVT. These are released by neutrophils and, in addition to trapping pathogens, can mediate the formation of deep vein thrombi, thereby blocking blood vessels and leading to the development of disease. Therefore, this paper describes the occurrence and development of NETs and discusses the mechanism of action of NETs on deep vein thrombosis. It aims to provide a direction for improved diagnosis and treatment of deep vein thrombosis in the near future.