Molecular Mechanisms of Histone-Induced Endotheliopathy in Trauma

创伤中组蛋白诱导内皮病的分子机制

• 批准号: 10541883
• 负责人: Kalev Freeman
• 金额: $ 39万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10541883
• 关键词: Acute; Biology; Blood; Blood Vessels; Blood flow; Clinical; Coagulation Process; Diagnosis; Disease; Endothelial Cells; Endothelium; Health; Health Care Costs; Histones; Impairment; Inflammation; Injury; Innate Immune Response; Intervention; Membrane; Molecular; Research; Role; Signal Transduction; Surface; Syndrome; Testing; Translating; Trauma; Trauma patient; Vascular Endothelium; burden of illness; endothelial dysfunction; improved; improved outcome; molecular modeling; novel strategies; programs; response; response to injury; therapeutic evaluation

Injury and trauma are common conditions that encompass a considerable burden of illness and account for a major component of health care costs. Endothelial cells (ECs) are the nexus between the blood and the body, and disruption of endothelial function in trauma leads to a syndrome of endothelipathy characterized by impaired microvascular blood flow, barrier integrity and coagulation. Our lack of understanding of how ECs translate the signals of trauma into changes in vasodilatory, barrier and coagulation functions represents a significant void— but also an opportunity for clinical intervention. The central theme of my lab is to understand endotheliopathy in trauma and inflammation, so that we can improve outcomes. This research program will deliver a molecular model of the mechanisms by which histones cause both immediate and sustained effects on vascular endothelium that explain oscillating clotting responses seen in trauma patients. This project will also test novel strategies to protect and/or rescue endothelial dysfunction after trauma. The proposed research is expected to significantly advance the continuum of research needed to improve diagnosis and management of acute endotheliopathy in trauma. Moreover, it has the potential to radically change our view of endothelial biology. This research will provide an enduring and sustained impact on understanding the role of the endothelium in health and disease.

伤害和创伤是涵盖大量疾病的常见疾病，并解释了 医疗保健费用的主要组成部分。内皮细胞（EC）是血液和身体之间的下一个， 创伤中内皮功能的破坏导致患有受损的内皮层状综合征 微血管血流，屏障完整性和凝结。我们缺乏对EC如何翻译的理解 因血管舒张，屏障和凝结功能变化而导致创伤的信号代表了一个重要的空隙 - 这也是临床干预的机会。我实验室的中心主题是了解内皮病 创伤和炎症，以便我们可以改善预后。该研究计划将提供分子 组蛋白对血管产生直接和持续作用的机制模型 内皮解释了创伤患者看到的振荡服装反应。这个项目还将测试小说 创伤后保护和/或救助内皮功能障碍的策略。拟议的研究有望 显着提高了改善急性诊断和管理所需的研究的连续性 创伤中的内皮病。此外，它有可能从根本上改变我们对内皮生物学的看法。这 研究将对了解内皮在健康中的作用产生持久和持续的影响 和疾病。