Project 5 - Cardiovascular Systems Area

项目5-心血管系统领域

• 批准号: 8883607
• 负责人: WALTER L MURFEE
• 金额: $ 25.51万
• 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 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8883607
• 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; 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.

微血管损失定义的微血管罕见，是微血管的解剖学损失，是 高血压。因为血压丧失伴随着针对的血压疗法 逆转稀疏代表了该疾病的候选治疗方法。但是，这种发展 疗法需要了解网络模式与 在衰老的时间过程中的微血管抗性和分子玩家的鉴定 负责网络增长受损。 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/静脉吻合术增加，表明 稀疏更为复杂，而仅仅是容器的损失。我们还观察到血管周细胞减少 神经元-GLIA抗原2（NG2）的表达，硫酸软骨素蛋白聚糖在功能上参与 血管生成。 NG2是内皮细胞增殖和迁移的积极调节剂，直接 影响存在的船只数量。我们的观察结果表明了一种新颖的分子摩卡 高血压期间的微血管稀疏。我们假设降低的NG2表达 高血压微血管网络导致建筑模式改变，导致升高 微血管抗性。为了检验这一假设，我们将使用 自发性高血压大鼠模型： AIM 1：确定微血管网络架构和NG2表达变化 自发性高血压大鼠衰老的过程。 目标2：确定NG2抑制作用足以改变微血管网络体系结构。 AIM 3：使用计算模型定量确定高血压改变的影响 微血管网络电阻的微血管网络体系结构。 这项工作的结果将为研究微血管之间的关系设定新的方向 高血压中的结构和升高的微伏脉抗性。