Comparison of RAS inhibitor classes for cerebrovascular management in hypertensive patients who contracted COVID-19 infection
感染 COVID-19 的高血压患者脑血管治疗中 RAS 抑制剂类别的比较
基本信息
- 批准号:10196006
- 负责人:
- 金额:$ 46.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-15 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:2019-nCoVACE2AffectAngiotensin IIAngiotensin II ReceptorAngiotensin ReceptorAngiotensin-Converting Enzyme InhibitorsAngiotensinsAntihypertensive AgentsBindingBloodBlood PressureBlood VesselsBrainBrain imagingCOVID-19COVID-19 patientCarbon DioxideCaringCerebrovascular CirculationCerebrovascular DisordersCerebrovascular systemCessation of lifeClinical TrialsCommunitiesConsumptionContractsControl GroupsCoupledDementiaDeteriorationDiabetes MellitusDiseaseElectroencephalogramElectrophysiology (science)Energy SupplyEnsureEnzyme Inhibitor DrugsEnzymesEquilibriumFunctional disorderFutureGoalsHealthcare SystemsHomeostasisHormone ReceptorHumanHypertensionImageImaging TechniquesIndividualInfectionIschemic StrokeLeadLisinoprilLosartanMagnetic Resonance ImagingMeasurementMeasuresMedicineMethodsModelingOutcomeParticipantPathway interactionsPatientsPharmaceutical PreparationsPharmacological TreatmentPhysiologicalPreventionProceduresProductionReceptor, Angiotensin, Type 1RegulationRenin-Angiotensin SystemResearchResearch ProposalsRestRiskRisk FactorsSARS-CoV-2 infectionSamplingShapesSignal TransductionSpin LabelsStimulusStrokeSurvivorsSystemTestingTimeType 2 Angiotensin II ReceptorVascular Dementiaacute careage relatedassaultblood oxygen level dependentblood oxygenation level dependent responseblood pressure regulationbrain tissuecerebrovascularclinical carecompare effectivenesscostdesignflexibilityfunctional magnetic resonance imaging/electroencephalographyhigh riskhypertension controlhypertension treatmentimaging modalityimaging studyinhibitor/antagonistinnovationmathematical analysismathematical methodsneural networkneurovascular couplingnovelpandemic diseasepathogenpreservationpreventrelating to nervous systemrespiratoryresponse
项目摘要
Abstract. It has become increasingly clear that the cerebrovascular system is under assault in many individuals
infected with COVID-19. In recent studies, patients with hypertension were found at a two-fold increased risk of
dying from COVID-19 infection, and 100% of infected patients who received a magnetic resonance imaging
(MRI) exam showed reduced CBF with 23% showing evidence indicative of ischemic stroke. The
cerebrovascular dysregulation due to COVID-19 may add to the already enormous burden of stroke and
dementia associated with age-related vascular deterioration. The pathogen SARS-CoV-2, causing COVID-19
illness, is now known to reduce function of an enzyme termed ACE2 that is a major regulator in the Renin-
Angiotensin system (RAS) that controls blood pressure and cerebral blood flow (CBF). This SARS-CoV-2
pathophysiology might lead to excessive stimulation of type 1 angiotensin receptor (AT1R) but reduced
stimulation of type 2 angiotensin receptor (AT2R), which is likely to both exacerbate hypertension and disrupt
CBF autoregulation and neurovascular coupling. Fortunately, two classes of currently available antihypertensive
medications are designed to regulate RAS by inhibiting AT1R. However, there may be a critical difference
between these two classes. Angiotensin II receptor blockers (ARBs) are protective of the pro-CBF activity on the
AT2R, and thus may be more effective at preventing the cerebrovascular dysregulation than the other class,
inhibitors of an enzyme termed ACE (ACEIs), which inhibit AT2R activity.
The goal of this R21 research proposal is to compare the effectiveness of ARB and ACEI antihypertensive
medicines in preventing long-term cerebrovascular dysregulation in hypertensive patients infected with COVID-
19. Two novel imaging methods recently developed in our lab will be leveraged to assess CBF autoregulation
and neurovascular coupling (NVC) at least 1 year after the severe infection. First, we will conduct noninvasive
optimized arterial spin labeling (ASL) MRI and respiratory challenge-weighted blood oxygenation level-
dependent (BOLD) MRI to measure baseline CBF and autoregulatory capacity in combination with novel
analyses that decouple the magnitude of vascular signal from contamination due to timing-related differences.
Second, we will acquire simultaneous resting-state electroencephalogram and BOLD MRI to estimate the body’s
capacity to adjust vascular energy delivery in response to changes in the demand from neural
electrophysiological activity. We will quantify this NVC with cutting-edge mathematical analysis that detects
transient states of network activity in EEG and models the time-concordant local BOLD MRI responses.
Successful implementation of this approach would offer sensitive measurement of CBF regulation in
hypertensive COVID-19 survivors and would indicate that one class of antihypertensive medication may be more
effective in CBF management in the face of COVID-19-related dysregulation, demonstrating urgency of clinical
trials of RAS inhibitors in hypertensive patients with COVID-19 to optimize future clinical care.
抽象的。越来越明显的是,许多人的脑血管系统正受到攻击
感染了 COVID-19。最近的研究发现,高血压患者患高血压的风险增加两倍
死于 COVID-19 感染,并且 100% 的感染患者接受了磁共振成像
(MRI) 检查显示 CBF 减少,其中 23% 显示有缺血性中风的证据。这
COVID-19 导致的脑血管失调可能会加重中风和本已巨大的负担
与年龄相关的血管恶化有关的痴呆症。引起 COVID-19 的病原体 SARS-CoV-2
现在已知,疾病会降低一种称为 ACE2 的酶的功能,ACE2 是肾素的主要调节因子。
控制血压和脑血流量(CBF)的血管紧张素系统(RAS)。这种 SARS-CoV-2
病理生理学可能导致 1 型血管紧张素受体 (AT1R) 过度刺激,但减少
刺激 2 型血管紧张素受体 (AT2R),这可能会加剧高血压并扰乱
CBF 自动调节和神经血管耦合。幸运的是,目前可用的抗高血压药物有两类
药物旨在通过抑制 AT1R 来调节 RAS。然而,可能存在关键差异
在这两个类之间。血管紧张素 II 受体阻滞剂 (ARB) 可以保护 CBF 前体的活性
AT2R,因此可能比其他类别更有效地预防脑血管失调,
称为 ACE (ACEIs) 的酶抑制剂,可抑制 AT2R 活性。
该 R21 研究提案的目标是比较 ARB 和 ACEI 降压药的有效性
预防感染新冠病毒的高血压患者出现长期脑血管失调的药物
19. 我们实验室最近开发的两种新型成像方法将用于评估 CBF 自动调节
严重感染后至少 1 年进行神经血管耦合 (NVC)。首先,我们将进行非侵入性的
优化的动脉自旋标记 (ASL) MRI 和呼吸挑战加权血氧水平 -
依赖 (BOLD) MRI 结合新颖的方法测量基线 CBF 和自动调节能力
由于时间相关的差异,将血管信号的幅度与污染分开的分析。
其次,我们将同时获取静息态脑电图和 BOLD MRI 来估计身体的
调节血管能量输送以响应神经需求变化的能力
电生理活动。我们将通过尖端数学分析来量化这种 NVC,以检测
EEG 中网络活动的瞬态并模拟时间一致的局部 BOLD MRI 响应。
该方法的成功实施将为 CBF 调节提供灵敏的测量
高血压 COVID-19 幸存者,这表明一类抗高血压药物可能更有效
面对与 COVID-19 相关的失调,CBF 管理有效,这表明临床的紧迫性
在患有 COVID-19 的高血压患者中进行 RAS 抑制剂试验,以优化未来的临床护理。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Meher R Juttukonda其他文献
Meher R Juttukonda的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Meher R Juttukonda', 18)}}的其他基金
Microvascular mechanisms underlying white matter lesions in older adults
老年人白质病变的微血管机制
- 批准号:
10301549 - 财政年份:2021
- 资助金额:
$ 46.2万 - 项目类别:
Microvascular mechanisms underlying white matter lesions in older adults
老年人白质病变的微血管机制
- 批准号:
10632109 - 财政年份:2021
- 资助金额:
$ 46.2万 - 项目类别:
Imaging Microvascular Hemodynamics In Older Adults With Varying Genetic Risk For Alzheimer's Disease
对具有不同阿尔茨海默病遗传风险的老年人进行微血管血流动力学成像
- 批准号:
10194991 - 财政年份:2021
- 资助金额:
$ 46.2万 - 项目类别:
Microvascular mechanisms underlying white matter lesions in older adults
老年人白质病变的微血管机制
- 批准号:
10491330 - 财政年份:2021
- 资助金额:
$ 46.2万 - 项目类别:
相似国自然基金
新型蝙蝠MERS簇冠状病毒HKU5的ACE2细胞受体识别及其分子机制研究
- 批准号:
- 批准年份:2024
- 资助金额:0.0 万元
- 项目类别:省市级项目
铁皮石斛通过肠道 ACE2 修复 Trp/GPR142 介
导“肠-胰岛 ”轴血糖调控功能的降糖机制研
究
- 批准号:Y24H280055
- 批准年份:2024
- 资助金额:0.0 万元
- 项目类别:省市级项目
人类ACE2变构抑制剂的成药性及其抗广谱冠状病毒感染的机制研究
- 批准号:82330111
- 批准年份:2023
- 资助金额:220 万元
- 项目类别:重点项目
CAFs来源的外泌体负性调控ACE2促进肾透明细胞癌癌栓新辅助靶向耐药的机制研究
- 批准号:82373169
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
新型蝙蝠MERS簇冠状病毒HKU5的ACE2受体识别及细胞入侵机制研究
- 批准号:32300137
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
基于AT2/ACE2/Ang(1-7)/MAS轴调控心脏-血管-血液系统性重构演变规律研究心衰气虚血瘀证及其益气通脉活血化瘀治法生物学基础
- 批准号:82305216
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
基于外泌体miRNAs介导细胞通讯的大豆ACE2激活肽调控血管稳态机制研究
- 批准号:32302080
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
感毒清经ACE2/Ang(1-7)/MasR信号通路抑制PM2.5诱导慢性气道炎症的机制:聚焦肺泡巨噬细胞极化与“胞葬”的表型串扰
- 批准号:82305171
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
刺参自溶引发机制中ACE2调控靶点的调控网络研究
- 批准号:32372399
- 批准年份:2023
- 资助金额:50 万元
- 项目类别:面上项目
Spike变异对新冠病毒抗原性及ACE2种属嗜性的影响研究
- 批准号:82272305
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
相似海外基金
新型コロナウイルス感染阻害能を有する抗ACE2抗体の阻害機構に関する構造基盤解明
阐明具有抑制新型冠状病毒感染能力的抗ACE2抗体抑制机制的结构基础
- 批准号:
24K09338 - 财政年份:2024
- 资助金额:
$ 46.2万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
ACE2のユビキチン化を介したコロナウイルス感染機構の解明と創薬への挑戦
通过ACE2泛素化阐明冠状病毒感染机制和药物发现的挑战
- 批准号:
22KJ2499 - 财政年份:2023
- 资助金额:
$ 46.2万 - 项目类别:
Grant-in-Aid for JSPS Fellows
ACE2阻害薬およびERK経路阻害薬による慢性腎炎進展抑制効果の検証
ACE2抑制剂和ERK通路抑制剂抑制慢性肾炎进展的效果验证
- 批准号:
23K14982 - 财政年份:2023
- 资助金额:
$ 46.2万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Large-scale compatibility assessments between ACE2 proteins and diverse sarbecovirus spikes
ACE2 蛋白和多种 sarbecovirus 尖峰之间的大规模兼容性评估
- 批准号:
10722852 - 财政年份:2023
- 资助金额:
$ 46.2万 - 项目类别:
一次線毛とコロナウイルス感染におけるACE2の役割の解明
阐明 ACE2 在原发菌毛和冠状病毒感染中的作用
- 批准号:
22KF0004 - 财政年份:2023
- 资助金额:
$ 46.2万 - 项目类别:
Grant-in-Aid for JSPS Fellows
The regulatory roles of ACE2 and its interaction with Nrf2 in arsenic-induced endothelial dysfunction in experimental and epidemiological studies
实验和流行病学研究中 ACE2 的调节作用及其与 Nrf2 的相互作用在砷诱导的内皮功能障碍中的作用
- 批准号:
23K16310 - 财政年份:2023
- 资助金额:
$ 46.2万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Role of ACE2 in the mechanism of intestinal regeneration
ACE2在肠道再生机制中的作用
- 批准号:
23K15078 - 财政年份:2023
- 资助金额:
$ 46.2万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Research and development of a novel pediatric anti-obesity medicine via ACE2 activation in DIZE
通过 DIZE 中 ACE2 激活研发新型儿科抗肥胖药物
- 批准号:
23K15417 - 财政年份:2023
- 资助金额:
$ 46.2万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Lung delivery of novel ACE2 variants for COVID-19
针对 COVID-19 的新型 ACE2 变体的肺部输送
- 批准号:
10483042 - 财政年份:2022
- 资助金额:
$ 46.2万 - 项目类别:
ACE2 on gut barrier dysfunction and BRB disruption
ACE2 对肠道屏障功能障碍和 BRB 破坏的影响
- 批准号:
10535485 - 财政年份:2022
- 资助金额:
$ 46.2万 - 项目类别:














{{item.name}}会员




