Arteriole/Venule Polarity in Adult Microvasculature

成人微脉管系统中的小动脉/微静脉极性

基本信息

批准号：
7502110
负责人：
Shayn Peirce-Cottler
金额：
$ 36.62万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-28 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7502110
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 Numbers 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 Thinking 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

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 Numbers 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 Thinking 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

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项目摘要

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）：成人生物体的微血管生长和重塑影响许多组织修复过程，并在许多人类疾病中起关键作用，包括下肢和下肢和冠状循环的系统性动脉高血压，慢性伤口和缺血性疾病。功能性血管网络的形成依赖于包括动脉，毛细血管和静脉的血管类型的规范，以及它们的适当连通性。对开发血管网络进行的研究提供了有关在胚胎中如何建立动脉/静脉（A/V）极性以及A/V极性如何影响生长过程的洞察力。但是，目前尚不清楚成人微脉管影响重塑中A/V极性的机制。由于适当的血管规范和连通性对于推动正常的微血管功能至关重要，因此我们建议测试以下假设，即分子在动脉和静脉上差异化的分子介导了成年的微血管重塑。具体的目标1将量化NG2与其他细胞表面标记（Ephb4和Ephrinb2）在静止和重塑成人微血管网络中的空间表达谱。特定的目标2将通过使用功能阻断抗体和使用NG2 - / - 小鼠来破坏NG2信号传导，确定NG2的A/V比表达是否是微血管重塑的功能调节剂。特定的目标3将确定在延迟伤口愈合模型（糖尿病小鼠）模型中，NG2表达是否相对于A/V极性失调，以及是否阻塞或消除NG2功能会导致伤口延迟的伤口愈合。这些目标有可能通过1）确定新型血管特异性靶标的重新血管化疗法的靶标，以及2）为工程组织有组织的血管化构建体生成新方法，这些方法可以通过刺激新的血管生长来恢复患病或受伤的组织。