HIV-Related Changes to the Central-Autonomic Network and Associated Risk for Hypertension

项目摘要 尽管外周血中的人类免疫缺陷病毒（HIV）受到抑制，但HIV感染的单核细胞 容易将病毒运输到中枢神经系统（CNS）。外周血单个核细胞上调 表达促炎细胞因子导致病毒在整个CNS中的神经毒性作用，包括 支持心脏自主调节的结构。这种促炎免疫细胞的迁移和浸润 在炎症性内皮血管疾病的发病机制中也是关键。儿茶酚胺信号 在脑血管和内皮功能障碍的恶性循环中起主要作用。强直性升高 血浆儿茶酚胺和促炎细胞因子水平与降低的 内皮祖细胞虽然交感神经-副交感神经失衡已被报道的患者 自艾滋病毒开始流行以来，心脏代谢疾病的患病率继续下降， 目前还没有正式的研究，以自主神经系统功能障碍的中枢控制， 艾滋病。这项研究提出了使用功能性神经成像来确定是否艾滋病毒和/或前- 高血压（前-HTN）通过改变心血管（CV）反应性， 控制心率和血压的结构内的大脑活动和连接。该研究旨在 在休息时、精神紧张时和愤怒沉思后检查这些机制。第二个目标是 一项研究旨在确定在这些状态下呼吸频率的变化是否可以提供心脏保护。 效果 候选人将通过fMRI扫描评估大脑功能活动，同时收集以下数据： 心率、持续血压和呼吸频率。候选人还将收集血液，以便 评估雌激素水平，并分离和计数内皮祖细胞（EPCs）和炎性细胞， 单核细胞候选人还将学习通过血流测量血管内皮功能的技术- 介导的肱动脉扩张。将从总共72名男性和72名女性中收集数据，年龄从 35至65岁，在补助金的第1-4年期间。将144名成年人的总样本平均分为4份， 组（36例HIV+ pre-HTN、36例HIV+ NTN、36例HIV- pre-HTN和36例HIV- NTN）。这将使候选人能够 确定HIV或HTN疾病过程是否与CV调节相关，同时控制生物学 相关变量，如细胞和血管内皮功能以及性激素的存在。 本研究的第二个目的是通过确定中枢-自主神经网络的可塑性， 是否操纵呼吸频率可以改变血压和心率反应性， 提到了行为操纵具体来说，压力反射和大脑网络的可塑性支持 心率、血压和呼吸的协调将在艾滋病毒的背景下进行评估， 前HTN疾病状态。该项目的数据将为R 01研究提供信息，该研究的重点是实施一项 呼吸干预，以降低艾滋病毒感染者患HTN的风险。

Project Summary Despite suppression of the Human Immunodeficiency Virus (HIV) in the periphery, HIV-infected monocytes readily traffic the virus to the central nervous system (CNS). Up-regulation of peripheral mononuclear cells expressing pro-inflammatory cytokines leads to neurotoxic effects of the virus throughout the CNS, including structures that support cardio-autonomic regulation. This migration and infiltration of pro-inflammatory immune cells is also key in the pathogenesis of inflammatory endothelial vascular disease. Catecholamine signaling plays a major role in this vicious cycle of cerebrovascular and endothelial dysfunction. Tonic elevation of plasma catecholamines and pro-inflammatory cytokine levels are linked to reduced colony-forming capacity of endothelial progenitor cells. Although sympathetic-parasympathetic imbalance has been reported in patients since the beginning of the HIV epidemic and prevalence of cardio-metabolic disease comorbidity continues to rise there has been no formal investigation into the central control of autonomic nervous system dysfunction in HIV. This study proposes the use of functional neuroimaging to determine whether HIV and/or pre- hypertension (pre-HTN) has an additive or interactive effect on cardiovascular (CV) reactivity via an altered brain activity and connectivity within structures that control heart rate and blood pressure. The study aims to examine these mechanisms at rest, during mental stress, and following anger rumination. A second goal of this study is to determine whether a change in respiratory rate during these states may provide a cardioprotective effect. The candidate will assess functional brain activity through fMRI scans while simultaneously gathering data on heart rate, continuous blood pressure, and respiratory rate. The candidate will also collect blood in order to assess estrogen levels, and to isolate and enumerate endothelial progenitor cells (EPCs) and inflammatory monocytes. The candidate will also learn the techniques to measure vascular endothelial function through flow- mediated dilation of the brachial artery. Data will be collected from a total of 72 men and 72 women, aged from 35 to 65 years, during Years 1-4 of the grant. The total sample of 144 adults will be divided equally into 4 groups (36 HIV+ pre-HTN, 36 HIV+ NTN, 36 HIV- pre-HTN, and 36 HIV- NTN. This will allow the candidate to determine whether HIV or HTN disease processes are linked to CV regulation while controlling for biologically relevant variables such as cellular and vascular endothelial function and presence of sex hormones. The secondary aim of this study is to assess the plasticity of this central-autonomic network by determining whether manipulation of breathing rate can alter blood pressure and heart rate reactivity during the afore- mentioned behavioral manipulations. Specifically, the plasticity of the baroreflex and brain networks supporting the coordination of heart rate, blood pressure, and respiration will be evaluated within the context of HIV and pre-HTN disease state. Data from this project will inform an R01 study focused on implementing a paced breathing intervention to reduce the risk of HTN in persons living with HIV.