PDF(Pubmed)
Abstract：
UNASSIGNED: Stent intimal hyperplasia leads to in stent restenosis and thrombosis. This study determined whether Fibulin-1 activity in smooth muscle cells (SMCs) contributes to stent restenosis or thrombosis.
UNASSIGNED: Stent implantation was conducted in a pig model. Target vessel samples were stained and analyzed by protein mass spectrometry. Cell experiments and Fibulin-1 SMC specific knockout mice (Fbln1SMKO) were used to investigate the mechanism of Fibulin-1 induced SMC proliferation and thrombosis.
UNASSIGNED: SMC proliferation and phenotypic transition are the main pathological changes of intimal hyperplasia in venous stents. Protein mass spectrometry analysis revealed a total of 67 upregulated proteins and 39 downregulated proteins in intimal hyperplasia after stent implantation compared with normal iliac vein tissues. Among them, Fibulin-1 ranked among the top proteins altered. Fibulin-1 overexpressing human SMCs (Fibulin-1-hSMCs) showed increased migration and phenotypic switching from contractile to secretory type and Fibulin-1 inhibition decreased the activity of SMCs. Mechanistically, Fibulin-1-hSMCs displayed increased levels of angiotensin converting enzyme (ACE) expression and angiotensin II signaling. Inhibition of ACE or angiotensin II signaling alleviated the migration of Fibulin-1-hSMCs. Using Fibulin-1 SMC specific knockout mice (Fbln1SMKO) and venous thrombosis model, we demonstrated that Fibulin-1 deletion attenuated intimal SMCs proliferation and thrombosis. Further, Fibulin-1 concentration was high in iliac vein compression syndrome (IVCS) patients treated with stent and was an independent predictor of venous insufficiency.
UNASSIGNED: Fibulin-1 promotes SMC proliferation partially through ACE secretion and angiotensin II signaling after stent implantation. Fibulin-1 plays a role in venous insufficiency syndrome, implicating the protein in the detection and treatment of IVCS.
UNASSIGNED: Stent implantation was conducted in a pig model. Target vessel samples were stained and analyzed by protein mass spectrometry. Cell experiments and Fibulin-1 SMC specific knockout mice (Fbln1SMKO) were used to investigate the mechanism of Fibulin-1 induced SMC proliferation and thrombosis.
UNASSIGNED: SMC proliferation and phenotypic transition are the main pathological changes of intimal hyperplasia in venous stents. Protein mass spectrometry analysis revealed a total of 67 upregulated proteins and 39 downregulated proteins in intimal hyperplasia after stent implantation compared with normal iliac vein tissues. Among them, Fibulin-1 ranked among the top proteins altered. Fibulin-1 overexpressing human SMCs (Fibulin-1-hSMCs) showed increased migration and phenotypic switching from contractile to secretory type and Fibulin-1 inhibition decreased the activity of SMCs. Mechanistically, Fibulin-1-hSMCs displayed increased levels of angiotensin converting enzyme (ACE) expression and angiotensin II signaling. Inhibition of ACE or angiotensin II signaling alleviated the migration of Fibulin-1-hSMCs. Using Fibulin-1 SMC specific knockout mice (Fbln1SMKO) and venous thrombosis model, we demonstrated that Fibulin-1 deletion attenuated intimal SMCs proliferation and thrombosis. Further, Fibulin-1 concentration was high in iliac vein compression syndrome (IVCS) patients treated with stent and was an independent predictor of venous insufficiency.
UNASSIGNED: Fibulin-1 promotes SMC proliferation partially through ACE secretion and angiotensin II signaling after stent implantation. Fibulin-1 plays a role in venous insufficiency syndrome, implicating the protein in the detection and treatment of IVCS.
摘要：
■支架内膜增生导致支架再狭窄和血栓形成。这项研究确定了平滑肌细胞（SMC）中的Fibulin-1活性是否有助于支架再狭窄或血栓形成。
■在猪模型中进行支架植入。将靶血管样品染色并通过蛋白质质谱分析。细胞实验和Fibulin-1SMC特异性敲除小鼠（Fbln1SMKO）研究Fibulin-1诱导SMC增殖和血栓形成的机制。
■SMC增殖和表型转变是静脉支架内内膜增生的主要病理变化。蛋白质质谱分析显示，与正常髂静脉组织相比，支架植入后内膜增生中共有67种上调的蛋白质和39种下调的蛋白质。其中,Fibulin-1在改变的蛋白质中排名最高。Fibulin-1过表达的人SMC（Fibulin-1-hSMC）显示出从收缩型到分泌型的迁移和表型转换增加，而Fibulin-1抑制降低了SMC的活性。机械上,Fibulin-1-hSMC显示血管紧张素转换酶（ACE）表达和血管紧张素II信号水平升高。ACE或血管紧张素II信号传导的抑制减轻了Fibulin-1-hSMC的迁移。采用Fibulin-1SMC特异性敲除小鼠(Fbln1SMKO)和静脉血栓形成模型,我们证明了Fibulin-1缺失减弱了内膜SMCs的增殖和血栓形成。Further,在接受支架治疗的髂静脉压迫综合征（IVCS）患者中，Fibulin-1浓度较高，并且是静脉功能不全的独立预测因子。
■Fibulin-1在支架植入后部分通过ACE分泌和血管紧张素II信号促进SMC增殖。Fibulin-1在静脉功能不全综合征中起作用，在IVCS的检测和治疗中涉及该蛋白。
■在猪模型中进行支架植入。将靶血管样品染色并通过蛋白质质谱分析。细胞实验和Fibulin-1SMC特异性敲除小鼠（Fbln1SMKO）研究Fibulin-1诱导SMC增殖和血栓形成的机制。
■SMC增殖和表型转变是静脉支架内内膜增生的主要病理变化。蛋白质质谱分析显示，与正常髂静脉组织相比，支架植入后内膜增生中共有67种上调的蛋白质和39种下调的蛋白质。其中,Fibulin-1在改变的蛋白质中排名最高。Fibulin-1过表达的人SMC（Fibulin-1-hSMC）显示出从收缩型到分泌型的迁移和表型转换增加，而Fibulin-1抑制降低了SMC的活性。机械上,Fibulin-1-hSMC显示血管紧张素转换酶（ACE）表达和血管紧张素II信号水平升高。ACE或血管紧张素II信号传导的抑制减轻了Fibulin-1-hSMC的迁移。采用Fibulin-1SMC特异性敲除小鼠(Fbln1SMKO)和静脉血栓形成模型,我们证明了Fibulin-1缺失减弱了内膜SMCs的增殖和血栓形成。Further,在接受支架治疗的髂静脉压迫综合征（IVCS）患者中，Fibulin-1浓度较高，并且是静脉功能不全的独立预测因子。
■Fibulin-1在支架植入后部分通过ACE分泌和血管紧张素II信号促进SMC增殖。Fibulin-1在静脉功能不全综合征中起作用，在IVCS的检测和治疗中涉及该蛋白。
