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        MiR-125a-5p ameliorates monocrotalineinduced pulmonary arterial hypertension by targeting the TGF-β1 and IL-6/STAT3 signaling pathways

        Zongye Cai,Jian Li,Qi Zhuang,Xueming Zhang,Ancai Yuan,Lan Shen,Kang Kang,Bo Qu,Yuanjia Tang,Jun Pu,Deming Gou,Jieyan Shen 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

        Pulmonary vascular remodeling due to excessive proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs) is the hallmark feature of pulmonary arterial hypertension (PAH). Recent evidence suggests that miR-125a-5p plays a role in a rat model of monocrotaline-induced PAH (MCT-PAH); however, the underlying mechanism is currently unknown. Here, we examined the expression profile of miR-125a-5p in MCT-PAH rats and investigated the putative therapeutic effect of miR-125a-5p using the miR-125a-5p agomir. In addition, the miR-125a- 5p agomir or antagomir was transfected into rat PASMCs, and proliferation and apoptosis were measured. Activity of the miR-125a-5p target STAT3 was measured using a luciferase reporter assay, and the expression of downstream molecules was measured using RT–qPCR and/or western blot analysis. Importantly, inducing miR-125a-5p expression in vivo slowed the progression of MCT-PAH by reducing systolic pulmonary arterial pressure, the Fulton index, and pulmonary vascular remodeling. Moreover, overexpressing miR-125a-5p inhibited the proliferation and promoted the apoptosis of PASMCs. In addition, stimulating PASMCs with TGF-β1 or IL-6 upregulated miR-125a-5p expression, whereas overexpressing miR-125a-5p reduced TGF-β1 and IL-6 production, as well as the expression of their downstream targets STAT3 and Smad2/3; in contrast, downregulating miR-125a-5p increased TGF-β1 and IL-6 production. Finally, a dual-luciferase reporter assay revealed that miR-125a-5p targets the 3′-UTR of STAT3, suppressing the downstream molecules PCNA, Bcl-2, and Survivin. Taken together, these findings suggest that miR-125a-5p ameliorates MCT-PAH in rats, has a negative feedback regulation with TGF-β1 and IL-6, and regulates the proliferation and apoptosis of PASMCs by directly targeting STAT3.

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        Endovascular Repair of Blunt Popliteal Arterial Injuries

        Shan Zhong,Xiquan Zhang,Zhong Chen,Peng Dong,Yequan Sun,Wei Zhu,Xiaolin Pan,Deming Qi 대한영상의학회 2016 Korean Journal of Radiology Vol.17 No.5

        Objective: To evaluate the feasibility and effectiveness of endovascular repair for blunt popliteal arterial injuries. Materials and Methods: A retrospective analysis of seven patients with clinical suspicion of popliteal arterial injuries that were confirmed by arteriography was performed from September 2009 to July 2014. Clinical data included demographics, mechanism of injury, type of injury, location of injury, concomitant injuries, time of endovascular procedures, time interval from trauma to blood flow restoration, instrument utilized, and follow-up. All patients were male (mean age of 35.9 ± 10.3 years). The type of lesion involved intimal injury (n = 1), partial transection (n = 2), complete transection (n = 2), arteriovenous fistula (n = 1), and pseudoaneurysm (n = 1). All patients underwent endovascular repair of blunt popliteal arterial injuries. Results: Technical success rate was 100%. Intimal injury was treated with a bare-metal stent. Pseudoaneurysm and popliteal artery transections were treated with bare-metal stents. Arteriovenous fistula was treated with bare-metal stent and coils. No perioperative death and procedure-related complication occurred. The average follow-up was 20.9 ± 2.3 months (range 18–24 months). One patient underwent intra-arterial thrombolysis due to stent thrombosis at 18 months after the procedure. All limbs were salvaged. Stent migration, deformation, or fracture was not found during the follow-up. Conclusion: Endovascular repair seems to be a viable approach for patients with blunt popliteal arterial injuries, especially on an emergency basis. Endovascular repair may be effective in the short-term. Further studies are required to evaluate the long-term efficacy of endovascular repair.

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