The Basis of Anthrax-Induced Vascular Damage

描述(由申请人提供)：感染炭疽芽孢杆菌会导致出血、组织肿胀和血栓形成，极大地导致炭疽病的患病和死亡。因此，我们的长期目标是开发针对这些事件背后的血管损伤的治疗方法。为了建立这些疗法的科学基础，这项提议将使用小鼠模型在结构和分子水平上表征炭疽热引起的血管损伤。在第一个目标中，我们将通过组织学时间进程研究来确定急性血管损伤的超微结构基础。作为这一目标的一部分，还将确定炭疽致命毒素和水肿性毒素对血管病理的贡献。第二个目标是通过分析和调节已知在其他系统中导致血管病理的通路，来探索血管损伤的生理学基础。为了与R21筹资机制的探索性保持一致，这一目标将调查一些可能的情况，从而使我们通过积极和消极的结果更全面地了解。作为这一探索的一部分，我们希望确定和测试新的治疗策略。

DESCRIPTION (provided by applicant): Infection with Bacillus anthracis leads to bleeding, tissue swelling, and thrombosis, contributing significantly to illness and death from anthrax. Therefore, our long-term objective is to develop therapies targeting vascular damage underlying these events. To establish the scientific basis for these therapies, this proposal will use a murine model to characterize anthrax-induced vascular damage at a structural and molecular level. In the first aim, we will define the ultrastructural basis for acute vascular damage through histological time course studies. As part of this aim, the contributions of anthrax lethal toxin and edema toxin towards vascular pathology will also be determined. The second aim will explore the physiological basis for vessel damage through analysis and modulation of pathways known to contribute to vascular pathology in other systems. In keeping with the exploratory nature of the R21 funding mechanism, this aim will survey a number of possible scenarios, thereby giving us a more complete understanding through both positive and negative findings. As part of this exploration, we hope to identify and test new therapeutic strategies.