Multi-Scale Modeling of Vascular Signaling Units
血管信号单元的多尺度建模
基本信息
- 批准号:10614418
- 负责人:
- 金额:$ 54.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-16 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAngiotensin IIAngiotensin II ReceptorArteriesBlood VesselsBlood flowCardiovascular DiseasesCell LineCellsCessation of lifeCommunitiesComplexComputer ModelsContractsCoupledCouplingDataDependenceDevelopmentDiameterDiglyceridesDihydropyridinesDiseaseElectrophysiology (science)EventExperimental ModelsFemaleG alpha q ProteinGeneral PopulationGoalsHealthHypertensionInositolLinkMedicalMembraneMesenteryModelingMolecularMuscle CellsMuscle TonusMuscle functionNutrientOxygenPRKCA genePathologicPatientsPermeabilityPharmaceutical PreparationsPhysiologic pulsePhysiologicalProtein KinaseProteinsReceptor SignalingReceptor, Angiotensin, Type 1RegulationSarcoplasmic ReticulumSex DifferencesSignal TransductionSmooth MuscleSmooth Muscle MyocytesSystemTestingVariantVascular Smooth MuscleWomanWorkblood pressure controlblood pressure regulationcardiovascular risk factorexperimental studyhypertension treatmenthypertensiveinorganic phosphatemalemenmodels and simulationmodifiable riskmortalitymulti-scale modelingnanonanometernanometer resolutionnovelnovel strategiesoperationpharmacologicprematurepreventprotein structurereceptorresponsesexsuperresolution imagingtreatment strategyvoltage
项目摘要
Project Summary
The function of arteries is to deliver oxygen and nutrients necessary to sustain the function and survival of every
cell in the body. Arterial diameter, a key determinant of blood flow, is finely tuned by the contractile state of the
smooth muscle cells lining the walls of these vessels. To date, however, models of myogenic control of arterial
smooth muscle tone have largely been based on data from male myocytes. Yet, recent data from our team
suggest that sex-specific features that determine the operation of arterial myocytes are attributable to differences
in the spatial organization of signaling complexes formed by the PKC-anchoring protein AKAP150 and CaV1.2
channels, and the manner in which they regulate smooth muscle contractility. Our findings challenge the general
applicability of a model for electrical and pharmacological control of the myogenic response based on data from
male myocytes and support the view that myogenic responses are differentially regulated in male and female
arteries. In this project, we implement a multi-scale systems approach that includes super-resolution imaging,
electrophysiology, and computational approaches to rigorously investigate the mechanisms controlling blood
flow through the male and female pial-parenchymal circulatory unit under physiological and pathological
conditions. Specific aim 1 is to establish the fundamental sex-specific mechanisms controlling Ca2+ influx via
CaV1.2 channels in vascular smooth muscle. Specific aim 2 is to determine the impact of the physical
organization of type 1 AngII receptors (AngIIR1), AKAP150, PKCα, and CaV1.2 channels on myogenic tone in
male and female arterial smooth muscle. Finally, in specific aim 3 we will investigate whether changes in the
number and molecular organization of CaV1.2 and AngIIR1/AKAP150/PKCα signaling units differentially alter
Ca2+ influx, arterial wall [Ca2+]i, and myogenic tone in male and female smooth muscle during the development
of hypertension. This work will lead to the first model of vascular smooth muscle function that incorporates sex-
specific variations in protein organization, electrical activity, and Ca2+ signaling during health and disease, which
could inform the development of rational strategies for the treatment of hypertension in male and female.
项目总结
项目成果
期刊论文数量(3)
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 }}
COLLEEN E CLANCY其他文献
COLLEEN E CLANCY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('COLLEEN E CLANCY', 18)}}的其他基金
Multi-Scale Modeling of Vascular Signaling Units
血管信号单元的多尺度建模
- 批准号:
10406687 - 财政年份:2021
- 资助金额:
$ 54.53万 - 项目类别:
Multi-Scale Modeling of Vascular Signaling Units
血管信号单元的多尺度建模
- 批准号:
10394236 - 财政年份:2020
- 资助金额:
$ 54.53万 - 项目类别:
Development of the Predictive NeuroCardiovascular Simulator
预测性神经心血管模拟器的开发
- 批准号:
10397892 - 财政年份:2018
- 资助金额:
$ 54.53万 - 项目类别:
Development of the Predictive NeuroCardiovascular Simulator
预测性神经心血管模拟器的开发
- 批准号:
10001997 - 财政年份:2018
- 资助金额:
$ 54.53万 - 项目类别:
Development of the Predictive NeuroCardiovascular Simulator
预测性神经心血管模拟器的开发
- 批准号:
10092300 - 财政年份:2018
- 资助金额:
$ 54.53万 - 项目类别:
Development of the Predictive NeuroCardiovascular Simulator
预测性神经心血管模拟器的开发
- 批准号:
10215080 - 财政年份:2018
- 资助金额:
$ 54.53万 - 项目类别:
相似海外基金
Early endothelial function activation by angiotensin II receptor blockers prevents vascular damage in a model of diabetes
血管紧张素 II 受体阻滞剂早期激活内皮功能可预防糖尿病模型中的血管损伤
- 批准号:
493141 - 财政年份:2023
- 资助金额:
$ 54.53万 - 项目类别:
Clinical benefits and mechanism of action of angiotensin-II receptor blocker on Cardiovascular remodeling in patients with repaired coarctation of aorta
血管紧张素II受体阻滞剂对主动脉缩窄修复患者心血管重塑的临床疗效及作用机制
- 批准号:
10734120 - 财政年份:2023
- 资助金额:
$ 54.53万 - 项目类别:
Targeting cancer-associated fibroblasts and tumour hypoxia with angiotensin II receptor blockers
使用血管紧张素 II 受体阻滞剂靶向癌症相关成纤维细胞和肿瘤缺氧
- 批准号:
445961 - 财政年份:2021
- 资助金额:
$ 54.53万 - 项目类别:
Operating Grants
Antitumor effect of HCC and exosome microRNA by angiotensin II receptor blockers and molecular target drugs
血管紧张素II受体阻滞剂和分子靶向药物对HCC和外泌体microRNA的抗肿瘤作用
- 批准号:
19K17401 - 财政年份:2019
- 资助金额:
$ 54.53万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Pleiotropic activation of endothelial function by angiotensin II receptor blockers is crucial to their protective anti-vascular remodeling effects
血管紧张素 II 受体阻滞剂对内皮功能的多效性激活对其保护性抗血管重塑作用至关重要
- 批准号:
411570 - 财政年份:2019
- 资助金额:
$ 54.53万 - 项目类别:
Heterogeneity of Angiotensin II Receptor Blockers in the inhibition of Marfan-associated Aortic Root Dilation Independent of Blood Pressure Effects
血管紧张素 II 受体阻滞剂抑制马凡相关主动脉根部扩张的异质性,与血压影响无关
- 批准号:
391615 - 财政年份:2018
- 资助金额:
$ 54.53万 - 项目类别:
Relationship between serum EETs concentrations and cardiovascular events in patients taking angiotensin II receptor blockers
服用血管紧张素II受体阻滞剂的患者血清EETs浓度与心血管事件的关系
- 批准号:
26460229 - 财政年份:2014
- 资助金额:
$ 54.53万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The development of new angiotensin II receptor vaccine
新型血管紧张素II受体疫苗的研制
- 批准号:
25870715 - 财政年份:2013
- 资助金额:
$ 54.53万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Central GRK5 modulation of Angiotensin II receptor expression in heart failure
GRK5 对心力衰竭中血管紧张素 II 受体表达的中枢调节
- 批准号:
8531707 - 财政年份:2012
- 资助金额:
$ 54.53万 - 项目类别:
Central GRK5 modulation of Angiotensin II receptor expression in heart failure
GRK5 对心力衰竭中血管紧张素 II 受体表达的中枢调节
- 批准号:
8397394 - 财政年份:2012
- 资助金额:
$ 54.53万 - 项目类别:














{{item.name}}会员




