A NON-INVASIVE METHOD FOR EVALUATING PULMONARY ENDOTHELIAL CELL APOPTOSIS AND ITS APPLICATION TO THERAPY IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

一种评估肺内皮细胞凋亡的非侵入性方法及其在慢性阻塞性肺疾病治疗中的应用

基本信息

批准号：
15590820
负责人：
KANAZAWA Hiroshi
金额：
$ 2.24万
依托单位：
OSAKA CITY UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

The imbalance of growth factors for angiogenesis in the lung represents a situation in which the expression or activity of one growth factor predominates over another, usually of opposing effect, within the same compartment such as alveolar septa and airway walls. Therefore, growth factors (e.g., VEGF, bFGF and HGF) and opposing factors (e.g., endostatin) should be measured within the various compartments of the lung. It is very important to characterize homeostasis of growth factors for angiogenesis in parenchymal and airway tissues of COPD. These findings may strongly support the new theory of vascular involvement in the processes of COPD. We will serially measure the concentrations of various growth factors for angiogenesis, oxidants and anti-oxidants in induced sputum, bronchoalveolar lavage and exhaled breath condensate. The effects of cigarette smoking on growth factor levels will be also evaluated. If angiogenic factors are required for maintenance of the alveolar compartment in patients with emphysema, one might expect angiogenic factors to be reduced, since there are fewer distal alveolar septa to require angiogenic factor-related signaling for maintenance. However, in chronic bronchitis, in which active abnormal airway remodeling is occurring, one would expect excessive growth factor levels. Currently, there is no evidence that known pharmacologic therapies change annual decline of lung function in COPD patients. However, our findings may lead to a new strategy for intervention in the processes of COPD, and tailor-made therapy for targeting of angiogenesis in alveolar septa and airway walls will for the treatment of individual COPD patients.

在肺中血管生成的生长因子的不平衡代表了一种情况，在这种情况下，一个生长因子的表达或活性主要占另一个生长因子（通常具有相反效应），例如肺泡隔和气道壁。因此，应在肺部的各个区室内测量生长因子（例如VEGF，BFGF和HGF）和相对因子（例如，内抑素）。表征COPD实质和气道组织血管生成的生长因子的体内稳态非常重要。这些发现可能强烈支持在COPD过程中血管参与的新理论。我们将在诱导的痰液，支气管肺泡灌洗和呼出的呼吸凝结物中的血管生成，氧化剂和抗氧化剂的各种生长因子的浓度序列测量。还将评估吸烟对生长因子水平的影响。如果需要血管生成因子来维持肺气肿患者的肺泡室，则可能会期望降低血管生成因子，因为较少的牙槽隔膜需要较少的肺泡因子需要血管生成因子相关的信号来维持。然而，在慢性支气管炎中，发生主动气道重塑的慢性支气管炎，人们会期望生长因子过多。当前，尚无证据表明已知的药理疗法会改变COPD患者肺功能的年度下降。但是，我们的发现可能会导致在COPD过程中进行干预的新策略，并量身定制靶向肺泡隔隔隔板和气道壁的血管生成的治疗方法，以治疗单个COPD患者。