Project 5 - Cardiovascular Systems Area

项目5-心血管系统领域

• 批准号: 8663298
• 负责人: WALTER L MURFEE
• 金额: $ 26.26万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8663298
• 关键词: Adult; Age; Aging; Anastomosis - action; Antibodies; Antigens; Area; Blocking Antibodies; Blood Pressure; Blood Vessels; Blood capillaries; Cardiovascular system; Cell Proliferation; Characteristics; Chondroitin Sulfate Proteoglycan; Complex; Computer Simulation; Data; Development; Disease; Endothelial Cells; Genetic Models; Goals; Growth; Harvest; Hypertension; Inbred SHR Rats; Instruction; Label; Length; Location; Measures; Mentors; Mesentery; Methods; Metric; Microcirculation; Microvascular Dysfunction; Modeling; Molecular; Muscle; Neuroglia; Neurons; Pathway interactions; Pattern; Pericytes; Regenerative Medicine; Research; Resistance; Structure; Testing; Time; Tissue Harvesting; Tissues; Venous; Work; age related; angiogenesis; arteriole; base; capillary; cell motility; computational network modeling; density; design; gain of function; hemodynamics; insight; network architecture; network models; normotensive; novel; restoration; venule

Microvascular rarefaction, defined by the anatomical loss of microvessels, is a common characteristic of hypertension. Because the loss of vessels accompanies elevated blood pressure therapies aimed at reversing rarefaction represent candidate treatments for the disease. However, the development of such therapies requires an understanding of the functional relationship between network patterns and microvascular resistance over the time course of aging and the identification of the molecular players responsible for the impaired network growth. Recent data by the PI suggests that microvascular networks in the adult spontaneously hypertensive rat have increased arterial/venous anastomoses indicating that rarefaction is more complex that just a loss of vessels. We also have observed reduced perivascular cell expression of Neuron-Glia Antigen 2 (NG2), a chondroitin sulfate proteoglycan functionally involved in angiogenesis. NG2 is a positive regulator of endothelial cell proliferation and migration and directly influences the number of vessels present. Our observations suggest a novel molecular meachanism for microvascular rarefaction during hypertension. We hypothesize that reduced NG2 expression in hypertensive microvascular networks results in altered architectural patterns leading to elevated microvascular resistance. In order to test this hypothesis, we will complete the following specific aims using the spontaneously hypertensive rat model: AIM 1: Determine the microvascular network architecture and NG2 expression alterations over the time course of aging in spontaneously hypertensive rats. AIM 2: Establish that NG2 inhibition is sufficient to alter microvascular network architectures. AIM 3: Use a computational model to quantitatively determine the effect of altered hypertensive microvascular network architectures on microvascular network resistance. The results from this work will set new directions for investigating the relationships between microvascular structure and elevated microvasuclar resistance in hypertension.

微血管稀疏，由微血管的解剖学损失定义，是以下疾病的一个共同特征： 高血压。因为血管的损失伴随着血压升高，旨在 逆转稀疏是该疾病的候选治疗方法。然而，这样的发展 治疗需要了解网络模式和 微血管阻力随衰老时间的变化以及分子参与者的识别 造成网络增长受损的原因。 PI 的最新数据表明，微血管网络 成年自发性高血压大鼠的动脉/静脉吻合增加，表明 稀疏比单纯的血管损失更为复杂。我们还观察到血管周围细胞减少 神经元胶质抗原 2 (NG2) 的表达，这是一种硫酸软骨素蛋白聚糖，功能上参与 血管生成。 NG2是内皮细胞增殖和迁移的正调节因子，直接调节内皮细胞的增殖和迁移。 影响存在的船只数量。我们的观察表明了一种新的分子机制 高血压期间微血管稀疏。我们假设 NG2 表达减少 高血压微血管网络导致结构模式改变，导致血压升高 微血管阻力。为了检验这个假设，我们将使用以下方法完成以下具体目标 自发性高血压大鼠模型： 目标 1：确定微血管网络结构和 NG2 表达随时间的变化 自发性高血压大鼠的衰老过程。 目标 2：确定 NG2 抑制足以改变微血管网络结构。 目标 3：使用计算模型定量确定改变高血压的影响 微血管网络结构对微血管网络阻力的影响。 这项工作的结果将为研究微血管之间的关系奠定新的方向。 高血压的结构和微血管阻力升高。