EFFECT OF MICROVASCULAR PATTERNING ALTERATIONS ON NETWORK RESISTANCE IN SPONTANE

微血管模式改变对自发网络阻力的影响

• 批准号: 8360260
• 负责人: WALTER L MURFEE
• 金额: $ 10.33万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360260
• 关键词: Adult; Anastomosis - action; Antigens; Biology; Blood Pressure; Cell Proliferation; Centers of Research Excellence; Chondroitin Sulfate Proteoglycan; Computer Architectures; Data; Development; Endothelial Cells; Functional disorder; Funding; Goals; Grant; Hypertension; Inbred SHR Rats; Laboratories; Modeling; National Center for Research Resources; Neuroglia; Neurons; Pattern; Pericytes; Principal Investigator; Publications; Renal Hypertension; Research; Research Infrastructure; Resistance; Resources; Source; Time; United States National Institutes of Health; Venous; Work; base; cell motility; cost; hemodynamics; hypertension treatment

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. BACKGROUND AND HYPOTHESIS: Hypertension is associated with an increase of microvascular resistance, in part due to structural rarefaction defined by the anatomical loss of microvessels. Given that elevated blood pressure is accompanied and in some cases preceded by this loss of microvessels, therapies aimed at reversing rarefaction represent candidate treatments for hypertension. However, assessing the potential for such therapies and fully understanding microvascular dysfunction during hypertension requires a further mechanistic understanding of the relationship between network patterns and microvascular resistance. Preliminary data from our laboratory suggests that networks in the adult spontaneously hypertensive rat are marked by vessel loss, arterial/venous anastomoses, and reduced perivascular cell expression of Neuron-Glia Antigen 2 (NG2), a chondroitin sulfate proteoglycan recently implicated in endothelial cell proliferation and migration. Based on these observations, we hypothesize that reduced perivascular NG2 expression in hypertensive microvascular networks results in altered architectural patterns leading to elevated microvascular resistance. The following specific aims using the spontaneously hypertensive rat model were proposed for this subproject. SPECIFIC AIMS: AIM 1: Evaluate microvascular network architecture and vessel-specific perivascular expression of NG2 over the time course of hypertension development. AIM 2: Determine if hypertensive microvascular network architectures result from altered perivascular NG2 expression. AIM 3: Determine the effect of hypertensive microvascular network architectures on microvascular network resistance and vessel specific hemodynamics. GOALS DURING YEAR 1 OF FUNDING For Year 1 of this subproject, we were allocated $55,607. The goals for Year 1 were to 1) collect additional preliminary data to be included in an R01 application; 2) conclude ongoing projects that would then result in an increase in the number of hypertension related publications in order to strengthen the feasibility of work proposed in an R01 application; and 3) submit an R01 application directly related to the proposed COBRE subproject.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 背景和假设： 高血压与微血管耐药性的增加有关，部分原因是微血管的解剖学损失所定义的结构稀有性。 鉴于血压伴随着升高，在某些情况下是微血管丧失之前，旨在逆转罕见的疗法代表了高血压的候选治疗方法。 但是，评估这种疗法的潜力并在高血压期间完全了解微血管功能障碍需要进一步的机械理解网络模式与微血管耐药性之间的关系。 我们实验室的初步数据表明，成年自发性高血压大鼠的网络以血管损失，动脉/静脉吻合术以及降低神经元-GLIA抗原2（NG2）的血管周细胞表达的降低，这是一种硫酸软糖蛋白硫酸盐蛋白蛋白蛋白蛋白蛋白蛋白蛋白蛋白蛋白，最近在内皮细胞延伸和迁移中涉及。 基于这些观察结果，我们假设高血压微血管网络中血管周围的NG2表达降低会导致建筑模式改变，从而导致微血管耐药性升高。 为此，提出了使用自发性高血压大鼠模型的以下特定目标。 具体目的： AIM 1：评估NG2在高血压发育时间内的微血管网络结构和血管特异性周围表达。 AIM 2：确定高血压微血管网络结构是否是由于周围NG2表达改变而导致的。 目标3：确定高血压微血管网络体系结构对微血管网络抗性和血管特异性血流动力学的影响。 资金第一年的目标 在本次项目的第一年中，我们分配了$ 55,607。 第1年的目标是1）收集将包含在R01应用程序中的其他初步数据； 2）总结了正在进行的项目，这将导致与高血压相关出版物的数量增加，以增强R01应用程序中提出的工作的可行性； 3）提交与拟议的鞋底副本直接相关的R01申请。