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

项目摘要 尽管人类免疫缺陷病毒(HIV)在外周受到抑制，但感染HIV的单核细胞 很容易将病毒传播到中枢神经系统(CNS)。外周血单核细胞表达上调 表达促炎细胞因子会导致病毒在整个中枢神经系统产生神经毒性作用，包括 支持心脏自主神经调节的结构。促炎性免疫的这种迁移和渗透 细胞在炎症性内皮血管疾病的发病机制中也起着关键作用。儿茶酚胺信号转导 在脑血管和内皮功能障碍的恶性循环中起着重要作用。提神提神 血浆儿茶酚胺和促炎细胞因子水平与集落形成能力降低有关 内皮祖细胞。尽管已有交感-副交感神经失衡的报道 自艾滋病毒流行以来，心脏代谢性疾病的流行继续 目前还没有关于自主神经系统功能障碍的中枢控制的正式调查。 爱滋病毒。这项研究建议使用功能神经成像来确定艾滋病毒和/或前病毒是否 高血压(HTN前)对心血管(CV)反应性有相加或交互作用，通过改变 大脑活动和控制心率和血压的结构内的连接性。这项研究旨在 在休息、精神压力和愤怒沉思之后，检查这些机制。这方面的第二个目标 一项研究是确定在这些状态下改变呼吸频率是否可以提供心脏保护 效果。 候选人将通过功能磁共振扫描评估大脑功能活动，同时收集数据 心率、持续血压和呼吸频率。候选人还将采集血液，以便 评估雌激素水平，分离和计数内皮祖细胞(EPC)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- 介入性的臂动脉扩张。数据将从总共72名男性和72名女性那里收集，年龄从 35年至65年，在赠款的第1至4年期间。总共144名成年人的样本将被平均分为4组 HIV+HTN组36例，HIV+NTN组36例，HIV-Pre-HTN组36例，HIV-NTN组36例。这将允许候选人 确定HIV或HTN疾病过程是否与CV调节有关，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。 这项研究的第二个目的是评估这个中枢-自主神经网络的可塑性 在此之前，控制呼吸频率能否改变血压和心率反应性 提到了行为操控。具体地说，压力感受器反射和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和艾滋病的背景下进行评估 HTN前疾病状态。来自该项目的数据将为R01研究提供信息，该研究侧重于实施PATED 呼吸干预以降低艾滋病毒携带者感染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.