Systems biology of lymphatic transport

淋巴运输的系统生物学

• 批准号: 8927855
• 负责人: LANCE L MUNN
• 金额: $ 59.59万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 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/8927855
• 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; Housing; Immune System Diseases; Immune response; 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; Pathology; Pathway interactions; Patients; Performance; Peripheral; Physiology; Play; Production; Pump; Reaction; Relaxation; Role; Specific qualifier value; Sterility; System; Systems Biology; Testing; Tissues; Water; drug candidate; effective therapy; fluid flow; interstitial; intravital imaging; lymph flow; lymph nodes; lymphatic pump; mathematical model; mouse model; multi-scale modeling; novel; novel strategies; pressure; prevent; public health relevance; response; simulation; treatment strategy; vasomotion

 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.