Role of Vasodilator Stimulated Phosphoprotein (VASP) during Hypoxia, Inflammation and Ischemia-Reperfusion Injury.

血管舒张刺激磷蛋白 (VASP) 在缺氧、炎症和缺血再灌注损伤中的作用。

• 批准号: 128859549
• 负责人: Professor Dr. Peter Rosenberger
• 金额: --
• 依托单位: Klinik für Anaesthesiologie und Intensivmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/128859549?language=en
• 关键词: Role; Vasodilator; Stimulated; Phosphoprotein; VASP

Limited oxygen availability (hypoxia) is the end result for a variety of pathological conditions, such as shock, sepsis and inflammation. Hypoxia and acute inflammatory processes results in conformational changes of the cytoskeleton. This process is associated with a disruption of cellular barriers, a mainstay of the human organism to defend its integrity and might result in organ dysfunction. Vasodilator phosphostimulated protein (VASP) is a crucial cytoplasmatic actin binding protein controlling paracellular permeability as well as activation of thrombocytes. VASP expression is reduced during periods of hypoxia resulting in reduced cellular endothelial and epithelial barrier function. This has significant implications on organ protection during periods of systemic inflammation and ischemia reperfusion-injury. Our preliminary data demonstrate a crucial role of VASP for the alveolar-capillary barrier during acute lung injury and during periods of hypoxia. VASP also has significant impact during myocardial, hepatic and gastrointestinal ischemiareperfusion injury and on gastrointestinal barrier properties. Therefore we propose here to investigate the role of VASP and VASP expression on the vascular integrity and organ function during periods of acute inflammation, hypoxia and ischemiareperfusion injury. Taken together, these studies are aimed to identify novel innate metabolic and transcriptional pathways to maintain organ function and integrity during conditions of hypoxia, acute inflammation and reperfusion-injury. Extensions of these findings will help to identify novel molecular targets in the treatment of critical illnesses.

有限的氧可用性（缺氧）是多种病理状况的最终结果，例如休克、脓毒症和炎症。缺氧和急性炎症过程导致细胞骨架的构象变化。这一过程与细胞屏障的破坏有关，细胞屏障是人类机体保护其完整性的支柱，并可能导致器官功能障碍。血管舒张剂磷酸刺激蛋白（VASP）是一种重要的细胞质肌动蛋白结合蛋白，控制细胞旁通透性以及血小板活化。在缺氧期间VASP表达减少，导致细胞内皮和上皮屏障功能降低。这对全身炎症和缺血再灌注损伤期间的器官保护具有重要意义。我们的初步数据表明，在急性肺损伤和缺氧期间，VASP对肺泡-毛细血管屏障起着至关重要的作用。VASP对心肌、肝脏和胃肠道缺血再灌注损伤以及胃肠道屏障特性也有显著影响。因此，我们在此研究VASP及其表达在急性炎症、缺氧和缺血再灌注损伤时对血管完整性和器官功能的作用。总之，这些研究的目的是确定新的先天代谢和转录途径，以维持器官功能和缺氧，急性炎症和再灌注损伤的条件下的完整性。这些发现的扩展将有助于确定治疗危重疾病的新分子靶点。