Targeting Inflammation to Treat Cardiovascular Aging in Humans
针对炎症治疗人类心血管衰老
基本信息
- 批准号:8702981
- 负责人:
- 金额:$ 18.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-08-01 至 2015-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdultAgeAge-YearsAgingAging-Related ProcessAnti-Inflammatory AgentsAnti-inflammatoryAntioxidantsAortaArteriesAscorbic AcidBiologicalBiological MarkersBlood VesselsCardiacCardiovascular DiseasesCardiovascular PhysiologyCardiovascular systemCause of DeathCentral ArteryCharacteristicsChronicClinicalComorbidityDeteriorationDevelopmentDiabetes MellitusDiseaseDouble-Blind MethodEffectivenessElderlyEndotheliumEpidemiologyFDA approvedFunctional disorderFundingFutureGoalsHeartHumanHypertensionImageImpairmentInflammationInflammatoryIntravenous infusion proceduresLeftLeft Ventricular FunctionLinkMediatingMorbidity - disease rateNational Institute on AgingOxidative StressPharmaceutical PreparationsPhysiologic pulsePhysiologicalPilot ProjectsPlacebo ControlPlacebosPlayPopulationPreventive InterventionProdrugsPropertyPublic HealthRandomizedRelaxationResearchRheumatoid ArthritisRiskRisk FactorsRoleSalineStructureTestingTherapeuticThoracic aortaTissuesTranslatingVasodilationVentricularWorkage relatedbasebrachial arterycardiovascular disorder riskefficacy testingelectric impedancefemoral arteryhigh riskimprovedinnovationinsightmortalitynormal agingnovelpreventpublic health relevancesalicylatesalicylsalicylic acidvascular inflammation
项目摘要
DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is the leading cause of death in the U.S. of which older age is a primary risk factor. Given that the number of adults >65 years of age in the U.S. will double to almost 70 million by 2030, future CVD-related illness in older adults remains a major public health concern. The increased risk of CVD in older adults has been attributed in large part to three fundamental alterations in cardiovascular structure and function associated with normal aging: stiffening of the large elastic central arteries (e.g., aort), reduction in vascular endothelial function, and decreased cardiac left ventricular (LV) diastolic function. The mechanisms responsible for these physiological changes with aging are not completely understood, but strong evidence suggests that inflammation and oxidative stress may be common mechanistic links between them. Our central working hypothesis is that chronic vascular inflammation plays a central role in the development of CVD with aging, through an oxidative stress-mediated deterioration in cardiovascular function. The broad, long-term objective of this project is to determine whether chronic inhibition of inflammation with salsalate
(8 weeks; 3-4 g/day), a non-acetylated salicylate commonly used clinically to treat chronic inflammatory diseases (e.g., rheumatoid arthritis), is effective in improving or restoring impaired
cardiovascular function in older adults through an oxidative stress-dependent mechanism. In a group of older adults (age 60-79 years) without CVD, we will test the following three specific aims in a randomized, placebo-controlled, double-blind, pilot study: Aim 1 will test the hypothesis that chronic inhibition of inflammation will improve aortic wall stiffness (carotid- femoral artery pulse wave velocity; proximal aortic characteristic impedance); Aim 2 will test the hypothesis that chronic inhibition of inflammation will improve vascular endothelial function (brachial artery flow-mediated endothelium-dependent vasodilation); and Aim 3 will test the hypothesis that chronic inhibition of inflammation will improve LV diastolic relaxation and filling
dynamics (diastolic LV mitral annular velocity, E' via Tissue Doppler imaging). We predict that the mechanism for the improvement in aortic stiffness, endothelial function, and LV diastolic function from inhibition of inflammation will be mediated in part by suppression of oxidative stress. The goals of this application are consistent with NIA's Strategic Direction that includes investigating "the role that inflammation plays in the aging process" and the current R21 funding announcement (PAS -11-280) testing "novel interventions for prevention and treatment of age related conditions." The study will have a significant impact on the field by: 1) establishing the efficacy of a FDA-approved anti-inflammatory drug on key physiological markers of cardiovascular aging strongly linked to clinical CVD risk; 2) offering preliminary insight into mechanisms of action by which salsalate has its effect on cardiovascular function in older adults, and 3) providing the scientific basis for future larger studies extending salsalate therapy
to older adults with age-related co-morbidities (e.g., hypertension, diabetes) and/or with clinical
CVD.
描述(由申请人提供):心血管疾病(CVD)是美国的主要死亡原因,其中老年是主要风险因素。鉴于美国65岁以上的成年人数量到2030年将翻一番,达到近7000万,未来老年人中的CVD相关疾病仍然是一个主要的公共卫生问题。老年人心血管疾病风险的增加在很大程度上归因于与正常衰老相关的心血管结构和功能的三个根本性改变:大型弹性中央动脉的硬化(例如,aort)、血管内皮功能降低和心脏左心室(LV)舒张功能降低。随着年龄的增长,这些生理变化的机制还没有完全了解,但有力的证据表明,炎症和氧化应激可能是它们之间的共同机制联系。我们的核心工作假设是,慢性血管炎症通过氧化应激介导的心血管功能恶化,在随着衰老的心血管疾病发展中发挥着核心作用。这个项目的广泛的、长期的目标是确定双水杨酸对炎症的慢性抑制作用是否
(8周; 3- 4g/天),一种临床上常用于治疗慢性炎性疾病(例如,类风湿性关节炎),有效改善或恢复受损的
通过氧化应激依赖性机制对老年人心血管功能的影响。在一组老年人中(年龄60-79岁)无CVD,我们将在随机、安慰剂对照、双盲、初步研究中测试以下三个具体目标:目标1将测试慢性抑制炎症将改善主动脉壁硬度的假设(颈动脉-股动脉脉搏波速度;近端主动脉特征阻抗);目标2将检验慢性抑制炎症将改善血管内皮功能(肱动脉血流介导的内皮依赖性血管舒张)的假设;目标3将检验慢性抑制炎症将改善LV舒张期舒张和充盈的假设
动力学(舒张期LV二尖瓣环速度,E',通过组织多普勒成像)。我们预测,抑制炎症改善主动脉僵硬度、内皮功能和左室舒张功能的机制将部分通过抑制氧化应激来介导。该申请的目标与NIA的战略方向一致,包括调查“炎症在衰老过程中的作用”和当前的R21资助公告(PAS-11 - 280)测试“预防和治疗年龄相关疾病的新干预措施”。“这项研究将通过以下方式对该领域产生重大影响:1)确定FDA批准的抗炎药对心血管衰老的关键生理标志物的疗效,这些标志物与临床CVD风险密切相关; 2)提供对双水杨酯对老年人心血管功能的作用机制的初步了解,以及3)为将来扩大双水杨酸酯治疗的更大规模研究提供科学依据
对于患有与年龄相关的合并症的老年人(例如,高血压、糖尿病)和/或临床
CVD。
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)
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Gary L. Pierce其他文献
Accuracy of a pretest questionnaire in exercise test protocol selection.
运动测试方案选择中预测试问卷的准确性。
- DOI:
- 发表时间:
2000 - 期刊:
- 影响因子:2.8
- 作者:
D. Bader;K. Mcinnis;T. E. Maguire;Gary L. Pierce;G. Balady - 通讯作者:
G. Balady
309 Aspirin decreases triglycerides in the development of preeclampsia
- DOI:
10.1016/j.ajog.2023.11.331 - 发表时间:
2024-01-01 - 期刊:
- 影响因子:
- 作者:
Kelsey Blocklinger;Tarynne E. Kinghorn;Kaylee Weaver;Ashlyn S. Mulcahey;Wendy S. Hamilton;Sydney Pearl;Meghan L. Funk;Dane D. Sweezer;Alexis J. Faudel;Sophia T. Schnoebelen;Amy K. Stroud;Stephen K. Hunter;Gary L. Pierce;Heath A. Davis;Boyd Knosp;Debra S. Brandt;Mark K. Santillan;Donna A. Santillan - 通讯作者:
Donna A. Santillan
Reduced cardiac baroreflex sensitivity is associated with greater aortic stiffness in middle-aged/older humans: Beneficial effect of habitual aerobic exercise
- DOI:
10.1016/j.artres.2014.09.022 - 发表时间:
2014-12-01 - 期刊:
- 影响因子:
- 作者:
Stephen A. Harris;Harald M. Stauss;Douglas R. Seals;Gary L. Pierce - 通讯作者:
Gary L. Pierce
Higher aortic stiffness and carotid systolic and pulse pressure are selectively associated with lower white matter integrity in the genu and frontal cortex in older healthy adults
- DOI:
10.1016/j.artres.2014.09.028 - 发表时间:
2014-12-01 - 期刊:
- 影响因子:
- 作者:
Lyndsey E. Dubose;Timothy B. Weng;Kaitlyn Dubishar;Merry Mani;Michelle W. Voss;Gary L. Pierce - 通讯作者:
Gary L. Pierce
Comparison of cardiopulmonary responses in obese women using ramp versus step treadmill protocols.
使用斜坡跑步机方案与步进跑步机方案比较肥胖女性的心肺反应。
- DOI:
10.1016/s0002-9149(98)00843-1 - 发表时间:
1999 - 期刊:
- 影响因子:0
- 作者:
K. Mcinnis;K. Mcinnis;D. Bader;Gary L. Pierce;G. Balady - 通讯作者:
G. Balady
Gary L. Pierce的其他文献
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{{ truncateString('Gary L. Pierce', 18)}}的其他基金
Sympathetic Regulation of Large Artery Stiffness in Humans with Age-Related Isolated Systolic Hypertension
年龄相关性单纯性收缩期高血压患者大动脉僵硬度的交感调节
- 批准号:
10400014 - 财政年份:2020
- 资助金额:
$ 18.88万 - 项目类别:
Sympathetic Regulation of Large Artery Stiffness in Humans with Age-Related Isolated Systolic Hypertension
年龄相关性单纯性收缩期高血压患者大动脉僵硬度的交感调节
- 批准号:
10620643 - 财政年份:2020
- 资助金额:
$ 18.88万 - 项目类别:
Targeting Inflammation to Treat Cardiovascular Aging in Humans
针对炎症治疗人类心血管衰老
- 批准号:
8583104 - 财政年份:2013
- 资助金额:
$ 18.88万 - 项目类别:
MOLECULAR MECHANISMS ASSOCIATED WITH CARDIOVASCULAR AGING
与心血管衰老相关的分子机制
- 批准号:
7719548 - 财政年份:2008
- 资助金额:
$ 18.88万 - 项目类别:
HUMAN AGING, EXERCISE AND ENDOTHELIUM-DEPENDENT VASODILATION: TRANSLATIONAL PHY
人类衰老、运动和内皮依赖性血管舒张:翻译物理
- 批准号:
7719552 - 财政年份:2008
- 资助金额:
$ 18.88万 - 项目类别:
RELATION BETWEEN ENDOTHELIAL-DEPENDENT DILATION AND SYSTEMIC AND LOCAL "PRO-OXI
内皮依赖性扩张与全身和局部“PRO-OXI”之间的关系
- 批准号:
7719557 - 财政年份:2008
- 资助金额:
$ 18.88万 - 项目类别:
ROLE OF TETRAHYDROBIOPTERIN DEFICIENCY IN CARDIOVASCULAR FUNCTION WITH AGING
四氢生物蝶呤缺乏对衰老过程中心血管功能的作用
- 批准号:
7719547 - 财政年份:2008
- 资助金额:
$ 18.88万 - 项目类别:
RELATION BETWEEN ENDOTHELIAL-DEPENDENT DILATION AND SYSTEMIC AND LOCAL "PRO-OXI
内皮依赖性扩张与全身和局部“PRO-OXI”之间的关系
- 批准号:
7604514 - 财政年份:2007
- 资助金额:
$ 18.88万 - 项目类别:
ROLE OF TETRAHYDROBIOPTERIN DEFICIENCY IN CARDIOVASCULAR FUNCTION WITH AGING
四氢生物蝶呤缺乏对衰老过程中心血管功能的作用
- 批准号:
7604497 - 财政年份:2007
- 资助金额:
$ 18.88万 - 项目类别:
HUMAN AGING, EXERCISE AND ENDOTHELIUM-DEPENDENT VASODILATION: TRANSLATIONAL PHY
人类衰老、运动和内皮依赖性血管舒张:翻译物理
- 批准号:
7604505 - 财政年份:2007
- 资助金额:
$ 18.88万 - 项目类别:
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