Enhancing parasympathetic activity to reduce vascular oxidative stress and endothelial dysfunction
增强副交感神经活性,减少血管氧化应激和内皮功能障碍
基本信息
- 批准号:10185061
- 负责人:
- 金额:$ 75.95万
- 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:2021-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:3-nitrotyrosineAcetylcholineAcetylcholinesterase InhibitorsAfrican AmericanAntigen-Presenting CellsArteriesAtherosclerosisBlindedBlood VesselsCaliberCardiovascular DiseasesCellsClinicalDataDevelopmentDoseEndothelial CellsEndotheliumEventF2-IsoprostanesFatty acid glycerol estersFunctional disorderGalantamineGoalsHarvestHispanicsImpairmentInflammationInflammation MediatorsInflammatoryInfusion proceduresIntercellular adhesion molecule 1IschemiaLipidsMeasuresMediatingMononuclearMorbidity - disease rateMusNADPNADPH OxidaseNerveNitric OxideNitric Oxide Signaling PathwayObesityOxidative StressParasympathetic Nervous SystemParticipantPathway interactionsPeripheralPeripheral Blood Mononuclear CellPlacebosPopulationProductionProteinsReactive Oxygen SpeciesSignal PathwaySkeletal MuscleSourceStudy SubjectSuperoxidesTestingUltrasonographyVasodilator AgentsWomanWorkadductbrachial arterycardiovascular disorder riskcholinergiccontrast enhancedcytokineeffective therapyendothelial dysfunctionexperiencehigh riskimmune activationimmunogenicimprovedinflammatory markermonocytemortalitynoveloxidationrandomized placebo controlled studyresponsethrombotictransmission processvascular bedvascular endothelial dysfunctionvascular inflammation
项目摘要
Project Summary
Endothelial dysfunction, a pro-thrombotic, inflammatory condition that causes impaired vascular reactivity is an
early reversible step in the development of atherosclerosis and cardiovascular disease (CVD). Multiple studies
consistently shown that African Americans (AAs) have impaired endothelial function compared to whites.
African Americans also experience disproportionately higher CV morbidity and 20% higher mortality than
whites or Hispanics. Endothelial dysfunction is caused by the overproduction of reactive oxygen species
(ROS), particularly superoxide which interferes with endothelial-derived nitric oxide signaling pathways. One of
the major sources of superoxide is NADPH oxidase; our previous work found that activation of NADPH oxidase
contributes to vascular oxidation through the formation of highly immunogenic isolevuglandins (IsoLG-protein
adducts) in peripheral mononuclear cells (PBMCs), which stimulates antigen presenting cells (APC) and
inflammatory mediators. Inflammation and oxidative stress are modulated by the parasympathetic nervous
system (PNS). We and others found that AAs have reduced PNS activity compared with whites. Our
preliminary data in obese AA women found that stimulation of the PNS cholinergic transmission with the
acetylcholinesterase inhibitor, galantamine, blocked the production of oxidative stress and inflammatory
cytokines induced by lipids. The overall goal of the current proposal is to determine if prolonged treatment with
galantamine improves endothelial dysfunction and vascular oxidative stress in AAs. For this purpose, we will
conduct a proof-of-concept, blinded, randomized, placebo-controlled study to test the effect of 3-month
treatment with galantamine (16 mg/day) on vascular oxidative stress and impaired vascular reactivity in AAs.
Specifically, we will evaluate whether galantamine treatment inhibits the activation of NADPH-IsoLG formation
and the subsequent immunogenic responses in PBMCs. Furthermore, we will determine if galantamine
decreases markers of oxidative stress and inflammation in harvested endothelial cells (ECs) and improves
vascular reactivity in the same study subjects. The planned studies will provide a comprehensive assessment
of the mechanism underlying the effect of increased PNS cholinergic transmission on endothelial dysfunction.
If our hypothesis is correct, and galantamine improves endothelial dysfunction in AAs, a population with a high
risk for CVD, we will discover a novel mechanism that could alter the oxidative and immunogenic responses in
this population and will offer a potential pathway for the development of more effective therapies aimed at
decreasing CVD.
项目总结
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 }}
Cyndya Adriana Shibao其他文献
Cyndya Adriana Shibao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('Cyndya Adriana Shibao', 18)}}的其他基金
Mentoring in cholinergic regulation of vascular oxidation
血管氧化的胆碱能调节的指导
- 批准号:
10664768 - 财政年份:2023
- 资助金额:
$ 75.95万 - 项目类别:
Mechanism of Glucose-dependent insulinotropic polypeptide (GIP) on Splanchnic Venous Capacitance in Postural Tachycardia Syndrome
葡萄糖依赖性促胰岛素多肽(GIP)对姿势性心动过速综合征内脏静脉电容的影响机制
- 批准号:
10669789 - 财政年份:2022
- 资助金额:
$ 75.95万 - 项目类别:
Mechanism of Glucose-dependent insulinotropic polypeptide (GIP) on Splanchnic Venous Capacitance in Postural Tachycardia Syndrome
葡萄糖依赖性促胰岛素多肽(GIP)对姿势性心动过速综合征内脏静脉电容的影响机制
- 批准号:
10522696 - 财政年份:2022
- 资助金额:
$ 75.95万 - 项目类别:
Obesity hypertension in African American women: Neuro-metabolic mechanisms
非裔美国女性肥胖高血压:神经代谢机制
- 批准号:
7962733 - 财政年份:2010
- 资助金额:
$ 75.95万 - 项目类别:
Obesity hypertension in African American women: Neuro-metabolic mechanisms
非裔美国女性肥胖高血压:神经代谢机制
- 批准号:
8473912 - 财政年份:2010
- 资助金额:
$ 75.95万 - 项目类别:
Obesity hypertension in African American women: Neuro-metabolic mechanisms
非裔美国女性肥胖高血压:神经代谢机制
- 批准号:
8269890 - 财政年份:2010
- 资助金额:
$ 75.95万 - 项目类别:
Obesity hypertension in African American women: Neuro-metabolic mechanisms
非裔美国女性肥胖高血压:神经代谢机制
- 批准号:
8131080 - 财政年份:2010
- 资助金额:
$ 75.95万 - 项目类别:
Obesity hypertension in African American women: Neuro-metabolic mechanisms
非裔美国女性肥胖高血压:神经代谢机制
- 批准号:
9271284 - 财政年份:2010
- 资助金额:
$ 75.95万 - 项目类别:
相似海外基金
Spatiotemporal dynamics of acetylcholine activity in adaptive behaviors and response patterns
适应性行为和反应模式中乙酰胆碱活性的时空动态
- 批准号:
24K10485 - 财政年份:2024
- 资助金额:
$ 75.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Structural studies into human muscle nicotinic acetylcholine receptors
人体肌肉烟碱乙酰胆碱受体的结构研究
- 批准号:
MR/Y012623/1 - 财政年份:2024
- 资助金额:
$ 75.95万 - 项目类别:
Research Grant
CRCNS: Acetylcholine and state-dependent neural network reorganization
CRCNS:乙酰胆碱和状态依赖的神经网络重组
- 批准号:
10830050 - 财政年份:2023
- 资助金额:
$ 75.95万 - 项目类别:
Study on biological significance of acetylcholine and the content in food resources
乙酰胆碱的生物学意义及其在食物资源中的含量研究
- 批准号:
23K05090 - 财政年份:2023
- 资助金额:
$ 75.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
alpha7 nicotinic acetylcholine receptor allosteric modulation and native structure
α7烟碱乙酰胆碱受体变构调节和天然结构
- 批准号:
10678472 - 财政年份:2023
- 资助金额:
$ 75.95万 - 项目类别:
Diurnal Variation in Acetylcholine Modulation of Dopamine Dynamics Following Chronic Cocaine Intake
慢性可卡因摄入后乙酰胆碱对多巴胺动力学调节的昼夜变化
- 批准号:
10679573 - 财政年份:2023
- 资助金额:
$ 75.95万 - 项目类别:
Striatal Regulation of Cortical Acetylcholine Release
纹状体对皮质乙酰胆碱释放的调节
- 批准号:
10549320 - 财政年份:2022
- 资助金额:
$ 75.95万 - 项目类别:
Differential Nicotinic Acetylcholine Receptor Modulation of Striatal Dopamine Release as a Mechanism Underlying Individual Differences in Drug Acquisition Rates
纹状体多巴胺释放的烟碱乙酰胆碱受体差异调节是药物获取率个体差异的机制
- 批准号:
10553611 - 财政年份:2022
- 资助金额:
$ 75.95万 - 项目类别:
Mechanisms of nicotinic acetylcholine receptor modulation of cocaine reward
烟碱乙酰胆碱受体调节可卡因奖赏的机制
- 批准号:
10672207 - 财政年份:2022
- 资助金额:
$ 75.95万 - 项目类别:
Structural basis of nicotinic acetylcholine receptor gating and toxin inhibition
烟碱乙酰胆碱受体门控和毒素抑制的结构基础
- 批准号:
10848770 - 财政年份:2022
- 资助金额:
$ 75.95万 - 项目类别: