잦은 천명 증상의 재발과 혈장 내 VEGF 및 plasmin 조절 인자들과의 관련성
Association Between Plasma Vascular Endothelial Growth Factor, Plasmin System Regulators and Recurrent Early Wheeze
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목 적 : Vascular endothelial growth factor (VEGF)는 혈관 생성과 염증 물질의 혈관투과성 증가의 기전에 중요한 역할을 하는 것으로 알려져 있으며 혈전 용해 작용을 방해하는 주된 물질인 plasminogen activator inhibitor-1 (PAI-1) 역시 혈관 생성을 자극한다고 알려져 있다. 최근의 보고에 의하면 천식 환자들에서 혈중 VEGF와 PAI-1이 함께 증가하는 양상이 관찰되고 있다. 저자들은 급성 천명 증상으로 입원한 환아들의 혈장내에서 sVEGF, PAI-1, tissue plasminogen activator (tPA) 및 endothelin (ET)-1 들이 증가하는지 관찰하였으며 천명 재발의 빈도와 관련하여 이들 측정치들의 차이가 있는지 알아보고자 하였다. 방 법 : 급성 천명 증상으로 소아과에 입원한 2세에서 6세 사이의 58명의 소아들을 대상으로 하였으며 이들을 입원 이전 1 년간의 천명 증상의 재발 빈도를 기준으로, 제 1군(3회 이상인 군, 34명)과 제 2군(1회 이하인 군, 24명)의 두 군으로 분류하였다. 두 환아군에서 입원시 채취한 혈액에서 혈장을 분리하였으며 ELISA 방법으로 sVEGF, PAI-1, ET-1, tPA의 농도를 측정하여 두 군간 그리고 같은 연령의 대조군(16명)과 비교하였다. 결 과 : 혈장 내 VEGF, PAI-1 및 tPA는 급성 천명 증상을 보인 환아군에서 대조군에 비해 유의하게 높았으며 제 1군에서 제 2군보다 유의하게 높은 측정치를 보였다. 그러나 ET-1는 환아군 간 또 대조군에 비해 유의한 차이를 보이지 않았다. 결 론 : VEGF와 plasmin system의 조절인자인 PAI-1 및 tPA는 잦은 천명의 재발을 나타내는 환아들에서 기도 염증 반응에 중요한 역할을 하며 이후 천식으로 진행하게 되는 기전에 기여할 가능성이 있음을 시사하는 것으로 생각된다.
Abstract
Purpose : Vascular endothelial growth factor (VEGF) is known to play an important role in the process of angiogenesis and chronic inflammation. Plasminogen activator inhibitor (PAI)-1 and tissue plasminogen activator (tPA) are main regulators of the plasmin system. The functions of these components are shown to be closely associated and recent studies have reported their potential roles in the asthmatic airways. We determined plasma levels of soluble VEGF (sVEGF), PAI-1, tPA and endothelin (ET)-1 in children with recurrent early wheeze. Our purpose was to examine whether there would be any difference in these biomarkers in relation to the relapse rate of wheezing. Methods : Fifty-eight children aged 2-6 years who were admitted with acute wheezing were enrolled. They were divided into two groups: patients with more than three relapses of wheezing (group 1, n=34) and those with less than one relapse (group 2, n=24). Plasma levels of sVEGF, PAI-1, ET-1 and tPA on admission were measured using ELISA in the two patient groups and controls (n=16). Results : PAI-1, sVEGF and tPA significantly increased during acute wheezing episode. The levels of these biomarkers were significantly higher in group 1 than in group 2 (P<0.01). ET-1 showed no significant difference between the patient groups and controls. Conclusion : Our study showed significantly elevated plasma levels of sVEGF and plasmin system regulators in children with recurrent early wheeze, which was even higher in the group with more frequent relapses. Our results suggest that these biomarkers may be associated with airway inflammation and may contribute to the later development of asthma in these children.
참고문헌 (27)
- "Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (flk-1) are expressed during vasculogenesis and vascular differentiation in the quail embryo", 169, pp.699~712 (1995)
- "The biology of vascular endothelial growth factor", 18, pp.4~25 (1997)
- "Vascular endothelial growth factor expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin through nuclear factor-kappa B activation in endothelial cells", 276, pp.7614~7620 (2001)
- "Gene expression of vascular endothelial growth factor and its receptor and angiogenesis in bronchial asthma", 107, pp.1034~1038 (2001)
- "VEGF effect on vascular permeability is mediated by synthesis of platelet-activating factor", 272, pp.H2746~H2756 (1997)
- "Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells", 95, pp.11709~11714 (1998)
- "induces plasminogen activators and plasminogen activator inhibitor-1 in microvascular endothelial cells", pp.902~6
- "The plasmin system in airway remodeling", 112, pp.1~7 (2003)
- "Plasminogen activator inhibitor-1 in the pathogenesis of asthma", 229, pp.138~146 (2004)
- "PAI-1 promotes extracellular matrix deposition in the airways of a murine asthma model", 294, pp.1155~1160 (2002)
- "Platelet function and fibrinolytic activity in patients with bronchial asthma", 11, pp.77~81 (2005)
- "Increased levels of vascular endothelial growth factor in induced sputum in asthmatic patients", 33, pp.595~599 (2003)
- "Expression of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin immunoreactivity in asthmatic airways and its relationship to angiogenesis", 107, pp.295~301 (2001)
- "Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung", 10, pp.1095~1103 (2004)
- "A potent antiangiogenic factor, endostatin prevents the development of asthma in a murine model", 116, pp.1220~1227 (2005)
- "Contribution of vascular endothelial growth factor to airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate-induced asthma", 168, pp.3595~3600 (2002)
- "A comparative study of two angiogenic factors: vascular endothelial growth factor and angiogenin in induced sputum from asthmatic children in acute attack", 129, pp.266~271 (2006)
- "Recurrent wheeze in early childhood and asthma among children at risk for atopy", 117, pp.e1132~e1138 (2006)
- "Early predictors for adult asthma and lung function abnormalities in infants hospitalized for bronchiolitis: a prospective 18-to 20-year follow-up", 27, pp.341~349 (2006)
- "Vascular endothelial growth factor-mediated induction of angiogenesis by human rhinoviruses", 117, pp.291~297 (2006)
- "Respiratory syncytial virus causes increased bronchial epithelial permeability", 126, pp.186~191 (2004)
- "three structurally and pharmacologically distinct isopeptides predicted by three separate genes", pp.2863~7
- "Endothelin-1-induced bronchoconstriction in asthma", 156, pp.382~388 (1997)
- "Endothelin-1 induces GM-CSF, IL-6 and IL-8 but not G-CSF release from a human bronchial epithelial cell line (BEAS-2B)", 30, pp.551~556 (1996)
- "The effects of endothelin-1 on degranulation, cytokine, and growth factor production by skin-derived mast cells", 34, pp.1910~1919 (2004)
- "Increased vascular endothelial growth factor may account for elevated level of plasminogen activator inhibitor-1 via activating ERK1", 2 in keloid fibroblasts, 2004, pp.286, C905~C912
- "Endothelin-1 enhances plasminogen activator inhibitor-1 production by human brain endothelial cells via protein kinase C-dependent pathway", 19, pp.1768~1775 (1999)
