Expressions and relationship of Krüppel-like factor 15 and endothelial nitric oxide synthase in experimental deep venous thrombosis

Abstract

Background: Deep vein thrombosis (DVT) is an early postoperative complication. Thrombosis formation, which is potentially life-threatening, seriously affects the rehabilitation of patients after surgery. We aimed to establish a C57 mouse model of DVT and to examine the changes in the expression of Krüppel-like factor 15 (KLF15) and endothelial nitric oxide synthase (eNOS) in venous wall tissues, and we also investigated the regulatory relationship of KLF15 and eNOS in the thrombin-induced human umbilical vein endothelial cell (HUVEC) injury cell model. Methods:The DVT model was established using the inferior vena cava (IVC) stenosis method. The expression levels of KLF15 and eNOS were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In cell experiments, the expression of KLF15 and eNOS was analyzed in the model of thrombin-induced HUVEC injury with KLF15 siRNA.Results: Compared to the control and sham-operated groups, KLF15 in the DVT group was upregulated, while eNOS was downregulated. The results of cell experiments revealed that KLF15 was downregulated in the thrombin+KLF15 siRNA group compared with the thrombin group. Meanwhile, eNOS was upregulated in the thrombin+KLF15 siRNA group compared with the thrombin group. These findings suggested that KLF15 regulated the expression of eNOS in the DVT model. Conclusions:We successfully constructed a DVT mouse model. In the early stage of DVT formation, KLF15 regulated the expression and inhibited the antithrombotic effect of eNOS, resulting in thrombi formation.

The Involvement of Krüppel-like Factors in Cardiovascular Diseases

“…Deep vein thrombosis (DVT) is a condition in which a clot obstructs blood flow, predominantly in the legs, and may require blood tinners, thrombolytics, support stockings, and in major cases, surgical care (thrombectomy) [ 95 ]. As earlier mentioned KLF proteins are known for networking to activate a proinflammatory phenotype in vascular structures.…”

“…In a thrombin-induced human umbilical vein endothelial cell (HUVEC) injury model, KLF-15, and endothelial nitric oxide synthase (Enos) were shown to be upregulated and downregulated, respectively. These findings resulted in thrombin formation due to inhibition of the antithrombotic effects of Enos by Klf-15 [ 95 ]. KLF-11 acts as main controller of the VSMCs procoagulant activity by binding to F3 to inhibit, which participates in the activation of the thrombotic phenotype.…”