Wendong Li

Downregulation of let-7e-5p contributes to endothelial progenitor cell dysfunction in deep vein thrombosis via targeting FASLG

This study aimed to evaluate the role of let-7e-5p in endothelial progenitor cells (EPCs) function and explore its therapeutic potential for deep vein thrombosis (DVT). We performed miRNAs screening and found that let-7e-5p was downregulated in DVT patients compared to control subjects. By using let-7e-5p agomir and antagomir, we demonstrated that let-7e-5p increased the migration and tube formation of human and rat EPCs. Based on bioinformatics, luciferase reporter assay and gene expression analysis, we identified Fas ligand (FASLG) as the target of let-7e-5p, and FASLG knockdown increased the migration and tube formation of EPCs. Furthermore, EPCs overexpressing let-7e-5p exhibited enhanced ability of homing and thrombus revascularization inrat model of venous thrombosis. In conclusion, let-7e-5p regulates the function of EPCs and is a potential therapeutic target in DVT treatment.

Autophagy protein 5 enhances the function of rat EPCs and promotes EPCs homing and thrombus recanalization via activating AKT

Deep venous thrombosis (DVT) is one of the most common peripheral vascular diseases. The roles of bone marrow-derived endothelial progenitor cells (EPCs) on the recanalization of venous thrombosis has been suggested recently, while the underlying mechanisms are not completely understood. Our objective was to investigate the functions of autophagy protein 5 (ATG5) in rat EPCs and its potential application in DVT. We have found that silencing of ATG5 or pharmacological suppression of ATG5 in rat EPCs reduces both the migration and psudotube formation under hypoxia in vitro. In line, overexpression of ATG5 significantly enhances the EPCs migration and psudotube formation capabilities. More importantly, injection of EPCs that stably express ATG5 increases EPC homing to the ischemic site and promotes thrombus recanalization in a rat DVT model in vivo. Mechanistically, we have shown that ATG5 overexpression enhances psudotube formation via the activation of AKT. These findings suggest that ATG5-AKT signaling plays an essential role in EPC migration and psudotube formation. Regulation of ATG5-AKT signaling may provide a potential novel therapy for DVT.

Safety and Efficacy of Low Dosage of Urokinase for Catheter-directed Thrombolysis of Deep Venous Thrombosis.

Background: Catheter-directed thrombolysis (CDT) has been a mainstay in treating deep venous thrombosis (DVT). However, the optimal dosage of a thrombolytic agent is still controversial. The goal of this study was to evaluate the safety and efficacy of low dosage urokinase with CDT for DVT. Methods: A retrospective analysis was performed using data from a total of 427 patients with DVT treated with CDT in our single center between July 2009 and December 2012. Early efficacy of thrombolysis was assessed with a thrombus score based on daily venography. The therapeutic safety was evaluated by adverse events. A venography or duplex ultrasound was performed to assess the outcome at 6 months, 1 year and 2 years postoperatively. Results: The mean total dose of 3.34 (standard deviation [SD] 1.38) million units of urokinase was administered during a mean of 5.18 (SD 2.28) days. Prior to discharge, Grade III (complete lysis) was achieved in 154 (36%) patients; Grade II (50–99% lysis) in 222 (52%); and Grade I (50% lysis) in 51 (12%). The major complications included one intracranial hemorrhage, one hematochezia, five gross hematuria, and one pulmonary embolism. Moreover, no death occurred in the study. Conclusions: Treatment of low-dose catheter-directed thrombosis is an efficacious and safe therapeutic approach in patients with DVT offering good long-term outcomes and minimal complications.

Resveratrol Improves Endothelial Progenitor Cell Function through miR-138 by Targeting Focal Adhesion Kinase (FAK) and Promotes Thrombus Resolution In Vivo

Background Endothelial progenitor cells (EPCs) were found to be a potential therapeutic choice for low extremity deep vein thrombosis. The aim of our research was to investigate the effect of resveratrol (RSV) on EPCs that may promote thrombus resolution and its potential pathway. Material/Methods EPCs were pretreated with RSV and migration; angiogenesis were evaluated ex vivo. Expression of miR-138 and focal adhesion kinase (FAK) was also tested. A murine model of venous thrombosis was developed as an in vivo model. The effects of RSV treatment on mice with inferior venous thrombosis were evaluated. Results We found that RSV increased EPCs migration and tube formation ex vivo. RSV significantly inhibited miR-138 expression. Moreover, we demonstrated that FAK was a target of miR-138 and revealed that FAK knockdown downregulated migration and angiogenesis of RSV-treated EPCs. In addition, RSV-induced EPCs promoted thrombus resolution in a murine model of venous thrombosis. Conclusions We found the first evidence that intravenous injection of RSV-treated EPCs enhanced thrombus resolution in vivo. RSV exerted its role by reducing miR-138 expression and therefore upregulated FAK.

Bidirectional Pull-Back Technique for Retrieval of Strut-Embedded Cylinder-Shaped Filters in Inferior Vena Cava

Background IVC filters have been widely accepted as an effective method to prevent pulmonary embolism (PE) in patients with deep venous thrombosis (DVT). However, the placement of IVC filters is associated with significant complications and filter retrieval can be challenging when the filter struts are embedded into the caval wall. Material/Methods Over 26 months, we reviewed the safety and efficacy of the bidirectional pull-back technique for removing strut-embedded IVC filters in 15 consecutive patients. Retrieval procedural data such as in-dwell time, retrieval time, and fluoroscopy time were recorded. Clinical outcomes and procedure-related complications were evaluated by venography or enhanced computed tomography. Histologic tissue was analyzed to reveal the pathologic effects of chronic filter implantation. All patients underwent routine clinical follow-up at a mean time of 12 months (range, 8–14 months). Results Technical success of filter retrieval was achieved in 100%, with mean implantation of 46.6 days (range, 27–66 days). Filter types were as follows: OptEase (n=11) and Aegisy (n=4). The mean retrieval time and fluoroscopy time were 21.43±5.42 min and 7.63±2.67 min, respectively. Immediate postprocedure venography showed no procedure-related complications. Thirteen patients discontinued previously prescribed lifelong anticoagulation. There were no long-term complications during follow-up. Conclusions The bidirectional pull-back technique is safe and efficient for filter retrieval. This complex technique can be particularly useful in selected patients to remove strut-embedded cylindrical-shaped IVC filters previously considered irretrievable.