Systems biology of lymphatic transport

淋巴运输的系统生物学

基本信息

批准号：
9279230
负责人：
LANCE L MUNN
金额：
$ 57.97万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9279230
关键词：
Adopted Adverse effects Affect Animal Model Bacterial Infections Beds Behavior Biological Calcium Calcium Channel Blockers Caliber Cardiovascular system Computer Simulation Diffusion Disease Drainage procedure Edema Equilibrium Failure Feedback Force of Gravity Frequencies Functional disorder Goals Heart Hindlimb Homeostasis Immune System Diseases Immune System and Related Disorders Immune response Impairment Individual Infection Inflammation Kinetics Knockout Mice Liquid substance Lymph Lymphatic Lymphatic System Lymphatic vessel Mechanics Mediating Modeling Morbidity - disease rate Movement Mus Nitric Oxide Nitric Oxide Signaling Pathway Pathologic Pathology Pathway interactions Patients Performance Peripheral Pharmacology Physiology Play Production Pump Reaction Relaxation Role Specific qualifier value Sterility System Systems Biology Testing Tissue Model Tissues Water drug candidate effective therapy fluid flow interstitial intravital imaging lymph flow lymph nodes lymphatic drainage lymphatic pump mathematical model mouse model multi-scale modeling novel novel strategies pressure prevent public health relevance response simulation targeted treatment treatment strategy vasomotion

项目摘要

DESCRIPTION (provided by applicant): Lymphatic vessels can transport fluid either by pressure-driven flow or by active pumping, even against gravity when necessary. In normal physiology, the lymphatic system is able to use these mechanisms to effectively and dynamically maintain tissue fluid homeostasis. In some diseases, however, lymphatic function is inefficient, resulting in tissue edema and weakened immune response. Because the mechanisms that control lymphatic function are not well-understood, we currently have no effective therapies that can restore lymphatic function in these patients. We propose that transport of lymph is controlled by complementary mechanobiological mechanisms involving Ca2+ fluxes and nitric oxide. We will test this hypothesis by developing a computational model of lymphatic transport and tissue fluid dynamics. We will then validate the simulations in a mouse model of lymphatic function and use it to identify and test novel treatments for edema and impaired lymph flow.

描述（由适用提供）：淋巴管可以通过压力驱动的流量或主动泵送运输流体，甚至在必要时在重力上进行。在正常生理学中，淋巴系统能够使用这些机制有效并动态维持组织液体稳态。然而，在某些疾病中，淋巴功能无效，导致组织水肿和免疫反应减弱。由于控制淋巴功能的机制不是很好的理解，因此我们目前没有有效的疗法可以恢复这些患者的淋巴功能。我们建议淋巴的运输受涉及Ca2+通量和一氧化氮的互补机械机制控制。我们将通过开发淋巴运输和组织流体动力学的计算模型来检验这一假设。然后，我们将验证淋巴功能的小鼠模型中的模拟，并使用它来识别和测试用于水肿和淋巴流量受损的新型治疗方法。