Exosomes in aging and operative hypothermic circulatory arrest

外泌体在衰老和手术低温停循环中的作用

• 批准号: 9766174
• 负责人: DAVID M ROTH
• 金额: $ 23.62万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766174
• 关键词: Address; Affect; Age; Aging; Anesthesia procedures; Apoptosis; Basic Science; Biological; Biological Markers; Biological Process; Blood; Blood Circulation; Brain; California; Cardiopulmonary Arrest; Cardiopulmonary Bypass; Cardiovascular system; Cell Survival; Cells; Cellular Immunity; Cellular Stress; Cellular Stress Response; Cessation of life; Characteristics; Clinical; Communication; Congenital Heart Defects; DNA; Data; Discipline; Endarterectomy; Endothelial Cells; Ensure; Event; Extracellular Space; Frequencies; Future; Growth Factor; Health Care Costs; Heart; Human; Institution; Investigation; Ischemia; Kidney; Lipid Bilayers; Lipids; Liquid substance; Liver; Lung; Malignant Neoplasms; Medicine; Metabolism; Monitor; Musculoskeletal System; Neuraxis; Operative Surgical Procedures; Patients; Perioperative; Perioperative Care; Population; Predisposition; Proteins; RNA; Renal Cell Carcinoma; Reperfusion Injury; Reperfusion Therapy; Research Design; Role; Signal Transduction; Site; Stimulus; Stress; Subgroup; Technology; Testing; Therapeutic; Thoracic aorta; Thromboendarterectomy; Time; Tissues; Universities; Vesicle; Work; age group; age related; aged; aging population; biomarker development; body system; chronic thromboembolic pulmonary hypertension; cold temperature; cytokine; design; exosome; extracellular vesicles; health care delivery; innovation; interest; novel; novel therapeutics; patient population; repaired; response; sex

ABSTRACT Aged patients are susceptible to cellular stress events associated with surgery. Exosomes represent a new paradigm in the cellular stress response that has only recently begun to be addressed in the surgical population. Exosomes are released by cells in response to numerous stimuli including cell stress and carry a cargo of biologically active molecules including DNA, RNA, proteins, lipids, cytokines, growth factors and metabolites. The role of exosomes in the aging surgical population is unknown and may have major impact on perioperative care. Deep hypothermic circulatory arrest (DHCA) is a profound perioperative stress event involving isolation of the systemic vasculature via cardiopulmonary bypass and arrest of the circulation to major organ systems. There is no information available regarding the release of exosomes as a result of the stress of whole body ischemia and reperfusion after DHCA in patients and most importantly as a function of age. At the University of California, San Diego we perform DHCA in conjunction with pulmonary thromboendarterectomy (PTE) surgery. Our clinical volume of 200 PTE surgeries per year results in patients with a range of ages (18- 80 years old) undergoing DHCA. We will test the novel hypothesis that surgically induced DHCA increases the release of exosomes, alters the characteristics of the exosome profile, and alters the ability of exosomes to affect cellular metabolism and function in an age dependent manner. In the proposal we will: 1) Determine the characteristics and content of exosomes released from patients before and after DHCA and address the potential role of patient age on the release and content of exosomes, and 2) Assess the potential of exosomes released from different age groups in response to DHCA to affect metabolism and function in human endothelial cells. The work will combine expertise from anesthesia, surgery, medicine and basic science disciplines and promote the future investigation of innovative hypotheses and novel therapies for the organismal response to ischemia-reperfusion injury in aged patients.

摘要 老年患者易受与手术相关的细胞应激事件的影响。外泌体代表了一种新的 细胞应激反应的范例，最近才开始在外科手术中得到解决。 人口外泌体由细胞响应于包括细胞应激在内的多种刺激而释放，并携带一种蛋白质。 生物活性分子的货物，包括DNA、RNA、蛋白质、脂质、细胞因子、生长因子和 代谢物。外泌体在老龄化手术人群中的作用尚不清楚，可能对老年人的生活产生重大影响。 围手术期护理。深低温停循环（DHCA）是一种严重的围手术期应激事件 包括通过心肺转流术隔离全身脉管系统和阻止循环到主要的 器官系统。没有关于由于压力而释放外泌体的信息。 DHCA后患者全身缺血和再灌注，最重要的是作为年龄的函数。在 加州大学圣地亚哥分校我们进行DHCA与肺动脉血栓内膜切除术 (PTE)手术我们每年200例PTE手术的临床量导致患者年龄范围（18- 80岁，正在接受DHCA。我们将测试新的假设，手术诱导DHCA增加 外泌体的释放，改变外泌体概况的特征，并改变外泌体 以年龄依赖性方式影响细胞代谢和功能。我们将：1）确定 DHCA前后从患者释放的外泌体的特征和含量，并解决 患者年龄对外泌体释放和含量的潜在作用，以及2）评估外泌体的潜力 从不同年龄组释放的DHCA，以影响人体的代谢和功能 内皮细胞这项工作将结合联合收割机的专业知识，从麻醉，外科，医学和基础科学 学科和促进未来的研究创新的假设和新的疗法， 老年患者对缺血再灌注损伤的机体反应。