Electrochemical Impedance to Access Metabolically Active Plaque
电化学阻抗接近代谢活跃斑块
基本信息
- 批准号:9274343
- 负责人:
- 金额:$ 39.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-07-10 至 2019-04-14
- 项目状态:已结题
- 来源:
- 关键词:AmericanAngiographyAnimal ModelApolipoprotein A-IArterial Fatty StreakAtherosclerosisCalcifiedCarotid ArteriesCathetersClinicalComputer SimulationCoronary arteryDetectionDiagnosticEarly DiagnosisElectrodesEventExhibitsFamily suidaeFatty acid glycerol estersFoam CellsFrequenciesFundingHigh Fat DietHistologicHumanImageryIndividualInflammatoryInflammatory ResponseInterventionKnock-outLesionLigationLipidsLiquid substanceLow Density Lipoprotein ReceptorMatrix MetalloproteinasesMeasuresMechanicsMetabolicMicroelectrodesModalityModelingMorbidity - disease rateMusMyocardial InfarctionNew ZealandNoduleOryctolagus cuniculusOxidative StressPatientsPredispositionPropertyRiskRuptureSOD2 geneSensitivity and SpecificitySignal TransductionSpecimenSpectrum AnalysisStrokeSubendothelial LayerSystemSystemic diseaseTestingTherapeutic EmbolizationTimeUltrasonic TransducerUltrasonographyVascular Endothelial CellVascular calcificationWestern Worldbiological adaptation to stresscalcificationcerebrovascularelectric impedancefemoral arteryin vivoinsightmacrophagemonocytemortalitymouse modelnoveloxidant stressoxidized lipidoxidized low density lipoproteinpeptidomimeticspercutaneous coronary interventionpublic health relevanceresponsesensorshear stress
项目摘要
DESCRIPTION (provided by applicant): Electrochemical Impedance to Assess Metabolically Active Plaque Atherosclerosis is a systemic disease; however, its manifestations tend to be focal and eccentric, and rupture of individual plaques is the primary underlying mechanism for myocardial infarction and stroke. Plaques prone to rupture contain high levels of inflammatory activity, due to oxidized lipids and foam cells. Fluid shear stress, in addition to its mechanical effects on vascular endothelial cells, promotes oxidative stress and inflammatory responses in plaque. However, real-time detection of the atherosclerotic lesions prone to rupture remains an unmet clinical challenge. Encouraging results from our previous exploratory R21 funding period demonstrated that integration of intravascular shear stress (ISS) and endoluminal electrochemical impedance spectroscopy (EIS) distinguishes pre-atherogenic lesions associated with oxidative stress in fat-fed New Zealand White (NZW) rabbits. Specifically, vessel walls harboring oxidized low density lipoprotein (oxLDL) exhibit distinct electrochemical impedance spectroscopy (EIS) magnitude, and that monocytes and oxLDL together destabilize calcific vascular nodules via induction of matrix metalloproteinase (MMP). In this context, we seek to develop an electrochemical strategy to identify culprit (albeit non-obstructive) lesions containing oxLDL-laden monocyte- macrophages (foam cells), during diagnostic angiography or percutaneous coronary intervention. We hypothesize that oxLDL-rich lesions harbor distinct electrochemical properties in the vessel wall that can be measured by frequency-dependent electrochemical impedance to identify metabolically active atherosclerotic lesions. Our hypothesis will be tested in three Specific Aims. Aim 1: Determine the mechanism by which oxLDL-rich lesions increase electrochemical impedance. EIS will be obtained in plaque from LDL receptor-knockout (LDLR-/-) mice. We hypothesize that it is the oxidant stress in the lesions that increases EIS magnitude. Aim 2: Determine in vivo sensitivity and specificity of EIS for oxLDL-laden, foam cell-rich lesions in fat-fed NZW rabbits as an established model of atherosclerosis with plaques accessible to catheter interrogation. We will also integrate three intravascular sensing modalities, shear stress (ISS), ultrasound (IVUS), and electrochemical impedance (EIS), for early detection of metabolically unstable lesions. Aim 3: Determine in vivo risk of rupture in high EIS plaque in a swine model. We will test whether high EIS lesions are prone to rupture and embolization, and we will assess whether the combination of high impedance and high shear predict lesion predisposition to embolization. Overall, our cross-disciplinary efforts aim to integrate electrochemical properties of active lipid-laden lesions with
three animal models and three sensing modalities to establish early detection of unstable lesions for patient-specific intervention.
描述(申请人提供):电化学阻抗用于评估代谢活跃的斑块动脉粥样硬化是一种全身性疾病;然而,其表现往往是局灶性和偏心性的,单个斑块的破裂是心肌梗死和中风的主要潜在机制。由于氧化的脂质和泡沫细胞,容易破裂的斑块包含高水平的炎症活动。流体剪切力,除了对血管内皮细胞的机械作用外,还促进斑块中的氧化应激和炎症反应。然而,容易破裂的动脉粥样硬化病变的实时检测仍然是一个尚未满足的临床挑战。我们之前的探索性R21资助期的令人鼓舞的结果表明,血管内切应力(ISS)和管腔内电化学阻抗谱(EIS)的整合可以区分脂肪喂养的新西兰白(NZW)兔与氧化应激相关的动脉粥样硬化前病变。具体地说,含有氧化型低密度脂蛋白(OxLDL)的血管壁表现出不同的电化学阻抗谱(EIS)幅度,单核细胞和oxLDL共同通过诱导基质金属蛋白酶(MMP)来破坏钙化性血管结节的稳定性。在此背景下,我们试图开发一种电化学策略,在诊断血管造影术或经皮冠状动脉介入治疗期间,识别含有oxLDL负载的单核巨噬细胞(泡沫细胞)的罪魁祸首(尽管是非梗阻性)病变。我们假设富含oxLDL的病变在血管壁具有不同的电化学性质,可以通过频率依赖的电化学阻抗来测量,以识别代谢活跃的动脉粥样硬化病变。我们的假设将在三个具体目标上得到检验。目的1:确定富含oxLDL的病变增加电化学阻抗的机制。EIS将从低密度脂蛋白受体基因敲除(LDLR-/-)小鼠的斑块中获得。我们假设是病变中的氧化应激增加了EIS的幅度。目的:以NZW兔动脉粥样硬化斑块为模型,研究EIS对脂肪喂养新西兰兔富含oxLDL泡沫细胞病变的敏感性和特异性。我们还将集成三种血管内传感手段,剪切力(ISS)、超声(IVUS)和电化学阻抗(EIS),以早期检测代谢不稳定的病变。目的3:在猪模型中确定高EIS斑块破裂的活体风险。我们将测试高EIS病变是否容易破裂和栓塞,我们将评估高阻抗和高剪切的组合是否预测病变易于栓塞。总体而言,我们的跨学科努力旨在将活性脂质损伤的电化学性质与
三种动物模型和三种传感方式,以建立不稳定病变的早期检测,以便针对患者进行干预。
项目成果
期刊论文数量(0)
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Tzung K Hsiai其他文献
Valentinuzzi ME: Understanding the Human Machine, A Primer for Bioengineering
- DOI:
10.1186/1475-925x-4-8 - 发表时间:
2005-02-10 - 期刊:
- 影响因子:3.200
- 作者:
Tzung K Hsiai - 通讯作者:
Tzung K Hsiai
Tzung K Hsiai的其他文献
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{{ truncateString('Tzung K Hsiai', 18)}}的其他基金
Integrating Volumetric Light-Field with Computational Fluid Dynamics to Study Myocardial Trabeculation and Function
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10626035 - 财政年份:2021
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Integrating Volumetric Light-Field with Computational Fluid Dynamics to Study Myocardial Trabeculation and Function
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10315583 - 财政年份:2021
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Integrating Volumetric Light-Field with Computational Fluid Dynamics to Study Myocardial Trabeculation and Function
将体积光场与计算流体动力学相结合来研究心肌小梁和功能
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Intravascular Deployment of a Wirelessly Powered Micro-Pacer
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10661490 - 财政年份:2020
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UCLA and Caltech integrated Cardiovascular Medicine for Bioengineers (iCMB)
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- 批准号:
10674980 - 财政年份:2020
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Intravascular Deployment of a Wirelessly Powered Micro-Pacer
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10358490 - 财政年份:2020
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$ 39.76万 - 项目类别:
UCLA and Caltech integrated Cardiovascular Medicine for Bioengineers (iCMB)
加州大学洛杉矶分校和加州理工学院生物工程师综合心血管医学 (iCMB)
- 批准号:
10038297 - 财政年份:2020
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$ 39.76万 - 项目类别:
UCLA and Caltech integrated Cardiovascular Medicine for Bioengineers (iCMB)
加州大学洛杉矶分校和加州理工学院生物工程师综合心血管医学 (iCMB)
- 批准号:
10202717 - 财政年份:2020
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UCLA and Caltech integrated Cardiovascular Medicine for Bioengineers (iCMB)
加州大学洛杉矶分校和加州理工学院生物工程师综合心血管医学 (iCMB)
- 批准号:
10469660 - 财政年份:2020
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Exercise-Induced Shear Stress Modulates Metabolic Pathways for Vascular Repair and Protection
运动引起的剪切应力调节血管修复和保护的代谢途径
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10265318 - 财政年份:2019
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