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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 背景和假设： 高血压与微血管阻力增加有关，部分原因是由微血管的解剖丢失所定义的结构稀疏。鉴于血压升高是伴随的，在某些情况下，微血管的丢失是高血压的候选治疗方法，旨在逆转稀疏性。然而，要评估这种治疗的可能性并充分了解高血压期间的微血管功能障碍，需要进一步从机制上理解网络模式和微血管阻力之间的关系。我们实验室的初步数据表明，在成年自发性高血压大鼠中，血管丢失、动/静脉吻合以及血管周围细胞神经胶质抗原2(NG2)的表达减少是显著的，NG2是一种最近参与内皮细胞增殖和迁移的软骨素蛋白多糖。基于这些观察，我们假设，高血压微血管网络中血管周围NG2表达的减少会导致结构模式的改变，从而导致微血管阻力增加。利用自发性高血压大鼠模型，为这一子项目提出了以下具体目标。 具体目标： 目的1：探讨NG2在高血压发病过程中的微血管网络构筑和血管特异性表达。 目的2：确定高血压微血管网络结构是否由血管周围NG2表达改变所致。 目的：探讨高血压微血管网络结构对微血管网络阻力和血管特异性血流动力学的影响。 第一年资助期间的目标 在这个分项目的第一年，我们得到了55607美元的拨款。第一年的目标是：1)收集额外的初步数据，以纳入R01申请；2)完成正在进行的项目，这些项目随后将导致高血压相关出版物数量的增加，以加强R01申请中提议的工作的可行性；以及3)提交与拟议的Cobre分项目直接相关的R01申请。