Integrative Neurobiology of Cardiovascular Regulation

描述（由申请人提供）：该计划项目资助继续专注于心血管调节的综合神经生物学。现在在其第40个年头，它代表了爱荷华州心血管研究中心的一个主要科学重点。这种更新的力量是基于其高级领导层的凝聚力和协同作用，其与新研究人员在概念和方法上的不断演变，以及从发现机制到将其转化为动物模型和人类疾病状态的连续努力。这四个项目代表了中枢神经激素过程的功能整合，这些过程通过涉及神经可塑性、氧化和炎症的相互依赖的分子机制诱导焦虑、高血压和血管损伤的病理状态。项目一：“Sites and Mechanisms of CNS Neuroplasticity in the Sensitization of Hypertension”（约翰逊，Kwitek）探索了通过上调关键脑核中的信号分子诱导高血压的机制，所述关键脑核包括控制血压的神经网络的血管紧张素/醛固酮敏感组分。项目二：“焦虑是否通过炎症和交感神经激活引起血管功能障碍？”（Haynes，Fiedorowicz，Pierce）认为外周和中枢（大脑）的血管功能障碍是炎症氧化过程的病理基础，炎症氧化过程增加了患有严重焦虑症的人的交感神经活动和心血管风险。项目三：“Neurohormonal Regulation of the Innate Immune System is Proinflammatory in a Genetic Model of Hypertension”（Abboud，Ballas，Zavazava）鉴定了胆碱能和ATI受体对具有血管和肾损伤的高血压中的炎性免疫病理过程的强烈调节影响。项目四：“Methylene Sulfoxide Reductase A：a novel Molecular Determinant of Autonomic Regulation and Hypertensive End-Organ Damage”（沙普洛，安德森，韦斯）探索了将氧化过程中的变化靶向特定脑部位和血管肌肉并从而改变高血压和血管病理过程的能力。探讨了高血压和血管病变中炎症和氧化过程的新概念。技术方法和动物模型已经很好地建立，并且在高血压、焦虑、自主神经功能障碍和血管病理学的分子机制方面存在主题翻译会聚。共同的思路创造了知识结构，其中综合的结果将远远大于组成部分的总和。

DESCRIPTION (Provided by applicant): This Program Project Grant continues to focus on Integrative Neurobiology of Cardiovascular Regulation. Now in its 40th year, it represents a major scientific emphasis of the Cardiovascular Research Center at lowa. The strength of this renewal is based on the cohesion and synergy of its senior leadership, its constant evolution in concepts and approaches with new investigators and the continuum of the effort from discovery of mechanisms to their translation into disease states in animal models and humans. The four projects represent a functional integration of central neurohormonal processes which through interdependent molecular mechanisms involving neuroplasticity, oxidation, and inflammation induce pathological states of anxiety, hypertension and vascular damage. Project I: "Sites and Mechanisms of CNS Neuroplasticity in the Sensitization of Hypertension" (Johnson, Kwitek) explores mechanisms that induce hypertension through the upregulation of signaling molecules in the key brain nuclei comprising the Angiotensin/Aldosterone sensitive components of the neural network controlling blood pressure. Project II: "Does Anxiety Cause Vascular Dysfunction Through Inflammation and Sympathetic Activation?" (Haynes, Fiedorowicz, Pierce) considers vascular dysfunction peripherally as well as centrally (cerebrally) as pathological underpinnings of an inflammatory oxidative process that increases sympathetic activity and cardiovascular risks in humans with severe anxiety. Project III: "Neurohormonal Regulation of the Innate Immune System is Proinflammatory in a Genetic Model of Hypertension" (Abboud, Ballas, Zavazava) identifies a strong regulatory influence of cholinergic and ATI receptors on the inflammatory immune pathological process in hypertension with vascular and renal damage. Project IV: "Methionine Sulfoxide Reductase A: a novel Molecular Determinant of Autonomic Regulation and Hypertensive End-Organ Damage" (Chapleau, Anderson, Weiss) explores the ability to target changes in the oxidative process to specific brain sites and vascular muscle and thereby alter the course of hypertension and vascular pathology. Novel concepts about inflammatory and oxidative processes in hypertension and vasculopathy are explored. The technical approaches and animal models are well established, and there is a thematic translational convergence of molecular mechanisms in hypertension, anxiety, dysautonomia and vascular pathology. Common threads create the intellectual fabric where the integrated outcome will be far greater than the sum of the components.