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.

损伤和外伤是常见病症，会带来相当大的疾病负担，并导致 医疗费用的主要组成部分。内皮细胞（EC）是血液和身体之间的纽带， 创伤中内皮功能的破坏会导致内皮病综合征，其特征是受损 微血管血流量、屏障完整性和凝血。我们对 EC 如何转化缺乏了解 创伤信号转化为血管舒张、屏障和凝血功能的变化代表着一个显着的空白—— 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，以便我们能够改善结果。该研究计划将提供分子 组蛋白对血管产生直接和持续影响的机制模型 内皮细胞解释了创伤患者中出现的振荡凝血反应。该项目还将测试小说 保护和/或挽救创伤后内皮功能障碍的策略。拟议的研究预计将 显着推进改善急性疾病诊断和管理所需的连续研究 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 研究将对理解内皮细胞在健康中的作用产生持久和持续的影响 和疾病。