Systems Biology of Angiogenesis: from Molecules to Therapy

血管生成的系统生物学：从分子到治疗

• 批准号: 7290922
• 负责人: BRIAN H ANNEX
• 金额: $ 39.46万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-27 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7290922
• 关键词: Amputation; Arterial Occlusive Diseases; Biology; Biomedical Engineering; Blood Vessels; Blood flow; Cell physiology; Cessation of life; Collaborations; Computer Simulation; Data; Diabetic mouse; Disease; Family; Goals; Growth; Health; Human; Investigation; Ligands; Macular degeneration; Malignant Neoplasms; Medical; Mus; Muscle; Myocardial Ischemia; Neurodegenerative Disorders; Normal tissue morphology; Obesity; Organism; Pathologic; Patients; Perfusion; Peripheral; Physiological; Public Health; Range; Research; Rheumatoid Arthritis; Scientist; Skeletal Muscle; Systems Biology; Therapeutic; Tissues; Universities; Vascular Endothelial Growth Factors; angiogenesis; design; improved; medical schools; neovascular; novel; receptor; therapeutic angiogenesis

DESCRIPTION (provided by applicant): Angiogenesis is defined as the growth of blood vessels from preexisting microvasculature. Therapeutic angiogenesis seeks to employ this phenomenon to treat patients with inadequate tissue perfusion by inducing neovascular growth. The goals of this project are: to develop anatomically-, biophysically-, and physiologically-detailed integrative multi-scale computational models of angiogenesis in normal and diseased skeletal muscle; to use highly synergistic and interactive computational and experimental approaches to understand physiologic and pathologic adaptations in mouse and human muscle; and to design improved and novel human therapeutics. Specifically, the experimentally-validated computational models will be used to understand, design and optimize therapies for human peripheral arterial obstructive disease (PAOD), a major cause of amputation and death. Currently there are no medical therapies available for PAOD that have the ability to increase perfusion and correct the principal abnormality of impaired blood flow. The vascular endothelial growth factor (VEGF) family of ligands and receptors will serve as the core focus of this project. To synthesize computational and experimental approaches, a collaboration has been established between computational biologists/bioengineers from Johns Hopkins University and basic/translational scientists from Duke University School of Medicine. Experimental data will be obtained from tissues of the normal and diabetic mouse and human with and without PAOD and the results will be utilized in multi-scale computational models, spanning from the molecule, to the tissue, to the organism level. The iteration of computational and experimental approaches will permit unparalleled investigation in the highly significant field of angiogenesis. This inter-disciplinary approach will have an immediate impact on fields that range from biology, to cell physiology, through human health and disease. The relevance of the research to public health would go beyond the applications to peripheral arterial obstructive disease, since over 70 diseases are presently identified as angiogenesis-dependent, including ischemic heart disease, cancer, macular degeneration, rheumatoid arthritis, obesity, and neurodegenerative diseases.

描述（由申请人提供）：血管生成被定义为血管从预先存在的微脉管系统生长。治疗性血管生成试图利用这种现象通过诱导新血管生长来治疗组织灌注不足的患者。该项目的目标是：开发正常和患病骨骼肌中血管生成的解剖学、生物物理和生理学详细的综合多尺度计算模型；使用高度协同和交互式的计算和实验方法来了解小鼠和人类肌肉的生理和病理适应；并设计改进和新颖的人类疗法。具体来说，经过实验验证的计算模型将用于理解、设计和优化人类外周动脉阻塞性疾病（PAOD）的治疗方法，这是截肢和死亡的主要原因。目前尚无可用于 PAOD 的药物疗法能够增加灌注并纠正血流受损的主要异常。血管内皮生长因子（VEGF）家族的配体和受体将作为该项目的核心焦点。为了综合计算和实验方法，约翰·霍普金斯大学的计算生物学家/生物工程师与杜克大学医学院的基础/转化科学家之间建立了合作。实验数据将从患有或不患有 PAOD 的正常和糖尿病小鼠和人类组织中获得，结果将用于从分子到组织再到生物体水平的多尺度计算模型。计算和实验方法的迭代将允许在血管生成这一高度重要的领域进行无与伦比的研究。这种跨学科方法将对生物学、细胞生理学、人类健康和疾病等领域产生直接影响。这项研究与公共卫生的相关性将超出外周动脉阻塞性疾病的应用范围，因为目前有 70 多种疾病被确定为血管生成依赖性疾病，包括缺血性心脏病、癌症、黄斑变性、类风湿性关节炎、肥胖和神经退行性疾病。