Upregulation of microRNA-136-5p Alleviates Acute Lower Extremity Deep Vein Thrombosis Through Negatively Regulating Interleukin-6 and C-Reactive

Background: Deep vein thrombosis (DVT) is known as a critical common health issue with high incidence, mortality, and long-term sequelae. Many differentially expressed microRNAs (microRNAs) have been proven to be promising prognostic markers for DVT patients. Herein, this study intended to explore the functional relevance of miR-136-5p on acute lower extremity DVT (LEDVT). Methods: Following the establishment of acute LEDVT rat model, the expression of miR-136-5p was altered by agomir or antagomir to assess its effects on regulating venous thrombus. Moreover, the gain- and loss-experiments, prior to the exposure to CoCl2, were performed in vitro to clarify the effects of miR-136-5p on human umbilical vein endothelial cell (HUVEC) apoptosis and levels of interleukin-6 (IL-6) and C-reactive protein (CRP). Results: Accordingly, miR-136-5p was found to be downregulated, while IL-6 and CRP were elevated in acute LEDVT patients. Conclusion: Notably, miR-136-5p was confirmed to target both IL-6 and CRP. Overexpression miR-136-5p led to reduced length, weight, and the ratio of weight to length of venous thrombus. Additionally, overexpressed miR-136-5p regulated both IL-6 and CRP to inhibit HUVECs apoptosis. Taken conjointly, the overexpression of miR-136-5p has the potential to bind to IL-6 and CRP to mitigate acute LEDVT, which provided new therapeutic targets for acute LEDVT treatment. Funding Statement: This study was supported by the General Projects of National Natural Science Foundation of China — the Function and Regulation Mechanism of ETBR in Aortic Endothelium and Smooth Muscle Cells in Pregnancy Induced Hypertension (No. 81871187), the Regional Projects of the National Natural Science Foundation of China — Correlation Analysis Between Endothelin Receptor and Pregnancy Induced Hypertension and Abnormal Blood Pressure Regulation (No. 81460239), and the Natural Science Foundation Project of Ningxia Province — Correlation Analysis Between Anastomotic Regional Blood Flow Velocity and Intimal Hyperplasia after Revascularization (No. NZ17195). Declaration of Interests: The authors have declared that no competing interests exist. Ethics Approval Statement: This study protocol was approved by the Ethics Committee and Experimental Animal Ethics Committee of Qingdao Municipal Hospital. In addition, written informed consent was obtained from all participants or their relatives that were involved in the study. The animal experiment strictly adhered to the principles of the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health to minimize the pain, suffering and discomfort to experimental animals.