Arteriole/Venule Polarity in Adult Microvasculature

成人微脉管系统中的小动脉/微静脉极性

• 批准号: 7820892
• 负责人: Shayn Peirce-Cottler
• 金额: $ 2.8万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7820892
• 关键词: Adult; Age; Animals; Antigens; Architecture; Automobile Driving; Blocking Antibodies; Blood; Blood Circulation; Blood Vessels; Blood capillaries; Cell Proliferation; Cell physiology; Cell surface; Cells; Characteristics; Chronic; Cornea; Coronary Circulation; Data; Diabetic mouse; Disease; Dorsal; Embryo; Engineering; Environment; Exhibits; Fibroblast Growth Factor 2; Gene Expression; Goals; Growth; Growth Factor; Hypertension; Immunohistochemistry; Impaired wound healing; Inflammation; Ischemia; Knockout Mice; Knowledge; Legal patent; Length; Link; Location; Lower Extremity; Mammals; Maps; Measures; Mediating; Methods; Microcirculatory Bed; Modeling; Molecular Profiling; Mus; Neuroglia; Neurons; Organism; Outcome; Pathologic Neovascularization; Pattern; Pericytes; Phenotype; Physiological; Play; Price; Process; Public Health; Rattus; Regulation; Relative (related person); Research Personnel; Retina; Role; Signal Transduction; Simulate; Skin; Smooth Muscle; Staining method; Stains; Stimulus; Stress; Subcutaneous Tissue; Surface; Testing; Time; Tissue Engineering; Tissues; Trees; Vascular Endothelial Growth Factors; Vascular remodeling; Vascularization; Venous; Wild Type Mouse; Work; Wound Healing; aged; angiogenesis; arteriole; capillary; cell type; clinically relevant; db/db mouse; density; design; diabetic; hemodynamics; human disease; in vivo; injured; innovation; insight; loss of function; novel; pressure; programs; research study; response; time use; tissue regeneration; venule

DESCRIPTION (provided by applicant): Microvascular growth and remodeling impact many tissue repair processes in the adult organism and play a critical role in a number of human diseases, including systemic arterial hypertension, chronic wounds, and ischemic disorders of the lower limbs and coronary circulations. The formation of a functional vascular network relies on specification of vessel types, including arterioles, capillaries, and venules, as well as their appropriate connectivity. Studies conducted on developing vascular networks have provided insight into how arterial/venous (A/V) polarity is established in the embryo and how A/V polarity impacts the growth process. However, the mechanisms by which A/V polarity in the adult microvasculature influence remodeling are currently not understood. Because proper vessel specification and connectivity is critical in driving normal microvascular function, we propose to test the hypothesis that molecules differentially present on arterioles and venules mediate adult microvascular remodeling. Specific Aim 1 will quantify the spatial expression profile of NG2 in relation to other cell surface markers of A/V polarity (EphB4 and ephrinB2) in quiescent and remodeling adult microvascular networks. Specific Aim 2 will determine if A/V specific expression of NG2 is a functional regulator of microvascular remodeling by disrupting NG2 signaling using a function-blocking antibody and using the NG2 -/- mouse. Specific Aim 3 will determine if NG2 expression is dysregulated with respect to A/V polarity in a model of delayed wound healing (the diabetic mouse), and if blocking or eliminating NG2 function contributes to delayed wound healing. These aims have the potential to enhance public health by 1) identifying novel vessel-specific targets for re-vascularization therapies and, 2) generating new methods for engineering organized vascularized constructs that can recover diseased or wounded tissues by stimulating new blood vessel growth.

描述（由申请人提供）：微血管生长和重塑影响成人有机体的许多组织修复过程，并在许多人类疾病中发挥关键作用，包括全身性动脉高血压、慢性伤口以及下肢和冠状循环的缺血性疾病。功能性血管网络的形成依赖于血管类型的规范，包括小动脉、毛细血管和小静脉，以及它们适当的连接性。对发育中的血管网络进行的研究深入了解了胚胎中动脉/静脉 (A/V) 极性如何建立以及 A/V 极性如何影响生长过程。然而，目前尚不清楚成人微脉管系统中 A/V 极性影响重塑的机制。由于适当的血管规格和连接性对于驱动正常的微血管功能至关重要，因此我们建议检验微动脉和微静脉上存在差异的分子介导成人微血管重塑的假设。具体目标 1 将量化静态和重塑成人微血管网络中 NG2 相对于 A/V 极性的其他细胞表面标记（EphB4 和 ephrinB2）的空间表达谱。具体目标 2 将通过使用功能阻断抗体和使用 NG2 -/- 小鼠破坏 NG2 信号传导来确定 NG2 的 A/V 特异性表达是否是微血管重塑的功能调节剂。具体目标 3 将确定伤口愈合延迟模型（糖尿病小鼠）中 NG2 表达是否在 A/V 极性方面失调，以及阻断或消除 NG2 功能是否会导致伤口愈合延迟。这些目标有可能通过以下方式增强公众健康：1）确定用于血运重建治疗的新的血管特异性靶点；2）产生用于工程组织化血管化结构的新方法，该结构可以通过刺激新血管生长来恢复患病或受伤的组织。