Fazeli Bahare, Rafatpanah Houshang, Ravari Hassan, Farid Hosseini Reza, Tavakol Afshari Jalil, Hamidi Alamdari Dariush, Valizadeh Narges, Moheghi Nasrin, Rezaee S A Rahim
Immunology Department, School of Medicine, Gonabad University of Medical Sciences, Mashhad, Iran.
Int J Rheum Dis. 2014 Jan;17(1):106-12. doi: 10.1111/1756-185X.12214.
The aim of this study was to investigate the impact of thromboangiitis obliterans (TAO) sera on activation of primary cultures of human umbilical vein endothelial cells (HUVECs) as a model for vascular endothelial cells.
Study subjects included 21 TAO patients as the case group and 20 healthy smokers and 17 healthy non-smokers as control groups. Case and control groups were matched based on their age, socioeconomic status and smoking habit. HUVECs were incubated with the sera of case and control groups and gene expression of intercellular adhesion molecule (ICAM-1) and vascular adhesion molecule (VCAM-1) were evaluated by real-time polymerase chain reaction, TaqMan method.
The expression of ICAM-1 and VCAM-1 were significantly higher in HUVECs after incubation with TAO sera compared to control groups (P < 0.05). VCAM-1 had a significant correlation with duration of smoking (P < 0.001, R = 0.672), while the expression of ICAM-1 had a significant correlation with the number of cigarettes smoked daily (P = 0.04, R = 0.421).
Sera from TAO patients could activate HUVECs. This same activation might occur in vivo by the responsible cytokines, in particular those released from activated platelets, free oxygen radicals, and possibly low levels of nitric oxide (NO) of the sera of TAO patients, as a consequences of chronic cigarette smoking and of endothelial NO synthase polymorphism. Therefore, plasma exchange might be helpful in acute phase of the disease for saving the limbs and administration the combinations of exogenous NO with anti-oxidants might be helpful in long-term management of TAO patients to reduce the risk and rate of amputation.
本研究旨在调查血栓闭塞性脉管炎(TAO)血清对人脐静脉内皮细胞(HUVECs)原代培养物激活的影响,以此作为血管内皮细胞的模型。
研究对象包括21例TAO患者作为病例组,20例健康吸烟者和17例健康非吸烟者作为对照组。病例组和对照组根据年龄、社会经济地位和吸烟习惯进行匹配。将HUVECs与病例组和对照组的血清一起孵育,采用实时聚合酶链反应(TaqMan法)评估细胞间黏附分子(ICAM-1)和血管黏附分子(VCAM-1)的基因表达。
与对照组相比,用TAO血清孵育后,HUVECs中ICAM-1和VCAM-1的表达显著更高(P<0.05)。VCAM-1与吸烟持续时间有显著相关性(P<0.001,R=0.672),而ICAM-1的表达与每日吸烟量有显著相关性(P=0.04,R=0.421)。
TAO患者的血清可激活HUVECs。这种相同的激活可能在体内由相关细胞因子引起,特别是那些从活化血小板释放的细胞因子、自由基,以及可能由于慢性吸烟和内皮型一氧化氮合酶多态性导致的TAO患者血清中低水平的一氧化氮(NO)。因此,血浆置换可能有助于疾病急性期挽救肢体,而给予外源性NO与抗氧化剂的组合可能有助于TAO患者的长期管理,以降低截肢风险和比率。