HIV-Related Changes to the Central-Autonomic Network and Associated Risk for Hypertension
HIV-Related Changes to the Central-Autonomic Network and Associated Risk for Hypertension
批准号:
10331310
负责人:
Roger Christopher McIntosh
金额:
$11.26万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-02-01 至 2024-01-31
关键词:
AIDS/HIV problemAddressAdultAmygdaloid structureAngerAnti-Retroviral AgentsArousalAutonomic nervous systemBaroreflexBehavior ControlBehavior TherapyBehavioralBloodBlood PressureBrainBreathingCardiometabolic DiseaseCardiovascular systemCatecholaminesCellsCerebrovascular DisordersDataDiseaseDistressDoctor of PhilosophyEndotheliumEpidemicEstrogensFlow CytometryFunctional Magnetic Resonance ImagingFunctional disorderGeneral PopulationGoalsGonadal Steroid HormonesGrantHIVHeartHeart RateHigh PrevalenceHypertensionImmuneIndividualInfiltrationInflammatoryInterventionInvestigationKnowledgeLearningLinkMeasurementMeasuresMediatingMononuclearNeuraxisNeuroimmuneNeuronal PlasticityParticipantPathogenesisPatientsPatternPeripheralPersonsPharmacotherapyPlasmaPlayPredispositionPrefrontal CortexPrevalenceProcessPsyche structurePublic HealthRecording of previous eventsRegulationReportingResearchRespirationRestRiskRoleSamplingScientistSignal TransductionSpecialistStressStructureTechniquesUp-RegulationVascular DiseasesVascular EndotheliumViral reservoirVirusWomanagedantiretroviral therapybasebrachial arterybrain dysfunctioncardioprotectioncareer developmentcomorbiditycytokineendothelial dysfunctionendothelial stem cellfunctional MRI scanheart rate variabilityhypertensiveindexingmenmigrationmonocyteneural networkneuroimagingneurotoxicnormotensiveprehypertensionprogramsrecruitrelating to nervous systemrespiratoryruminationsupport network
中文摘要
项目总结
英文摘要
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.
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DOI:
10.1016/j.jpsychores.2021.110403
发表时间:
2021-05
期刊:
Journal of psychosomatic research
影响因子:
4.7
作者:
[McIntosh R, Ironson G, Krause N]
通讯作者:
Krause N
DOI:
10.1038/s41371-020-00476-2
发表时间:
2021-12
期刊:
Journal of human hypertension
影响因子:
2.7
作者:
[McIntosh RC, Lobo JD, Yang A, Schneiderman N]
通讯作者:
Schneiderman N
Reply to "The insular cortex and QTc interval in HIV+ and HIV- individuals: Is there an effect of sympathetic nervous system activity?"
回复“HIV 和 HIV-个体的岛叶皮质和 QTc 间期:交感神经系统活动是否有影响?”
DOI:
10.1016/j.clinph.2017.10.017
发表时间:
2018
期刊:
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
影响因子:
--
作者:
[McIntosh,RogerC, Chow,DominicC, Lum,CoreyJ, Shikuma,CeciliaM, Kallianpur,KalpanaJ]
通讯作者:
Kallianpur,KalpanaJ
DOI:
10.1007/s10461-021-03462-y
发表时间:
2022-04
期刊:
AIDS and behavior
影响因子:
4.4
作者:
[Banerjee N, Goodman ZT, McIntosh R, Ironson G]
通讯作者:
Ironson G
DOI:
10.1016/j.ijpsycho.2021.01.019
发表时间:
2021-06
期刊:
International journal of psychophysiology : official journal of the International Organization of Psychophysiology
影响因子:
--
作者:
[McIntosh RC, Khambaty T, Llabre MM, Perreira KM, Gonzalez HM, Kansal MM, Tarraf W, Schneiderman N]
通讯作者:
Schneiderman N
共 6 条
Psycho-neuro-immune Mechanisms Linking Stigma and Discrimination to Carotid Plaque Formation in Persons living with HIV
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批准号:10762603
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项目类别:
-
资助金额:$70.89万
-
财政年份:2023
-
负责人:Roger Christopher McIntosh
-
依托单位:
海外基金