Dual Role of HSP70 in Diabetes-Induced Vascular Dysfunction
HSP70 在糖尿病引起的血管功能障碍中的双重作用
基本信息
- 批准号:10515009
- 负责人:
- 金额:$ 43.42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-04 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAgonistAnimalsAntibodiesAortaAtomic Force MicroscopyAutomobile DrivingBiologyBiomedical EngineeringBlood VesselsCell AdhesionCell CompartmentationCellsChronologyCollaborationsConfocal MicroscopyCultured CellsDataDepositionDiabetes MellitusDiseaseEngineeringEnvironmentEnzyme-Linked Immunosorbent AssayExposure toExtracellular MatrixFemaleFloridaGlucoseHealthHeat-Shock Proteins 70HumanHyperglycemiaITPR1 geneImmune systemImmunoglobulin GIn VitroInflammationInterleukin-1 betaInterleukin-6LaboratoriesLinkLiteratureMeasuresMesenteryMethodsMolecularMolecular ChaperonesMusNADPH OxidaseNon-Insulin-Dependent Diabetes MellitusOutcomeOutcomes ResearchOxidative StressPharmaceutical PreparationsPharmacologyPhysiologic pulsePhysiologicalPlayProteinsResearchResearch TrainingRho-associated kinaseRoleScienceSerumSeveritiesSignal TransductionSmall Interfering RNASmooth MuscleSmooth Muscle MyocytesSourceStudentsSupervisionTNF geneTechniquesTestingThermogenesisTissuesTransforming Growth Factor betaUltrasonographyUp-RegulationVascular DiseasesVascular Smooth MuscleWestern Blottingarterial stiffnessbasecytokinedb/db mousediabetes managementexperienceexperimental studyextracellularin vivoinhibitorinnovationknock-downmalemouse modelmultidisciplinarynanoscalepreventprofessorresponsesexultrasoundundergraduate student
项目摘要
Dual role of HSP70 in diabetes-induced vascular dysfunction
R15 – Applicant Kenia Nunes
Project Summary/Abstract
Vascular damage, a significant health problem, is linked to hyperglycemia, a key component of
both types of diabetes. The rationale for this study is that increased glucose levels chronologically
associate with higher levels of circulating Heat-shock protein 70 (HSP70), an intriguing molecular
chaperone that co-exists in different cell compartments and exerts antagonistic actions. There is
a well-known crosstalk between HSP70 and Ca2+, but not in smooth muscle. Only recently, my
lab showed that a functional iHSP70 is required for adequate vascular reactivity under
physiological conditions, as it impacts Ca2+ handling mechanisms. In diabetes, there is an
increase in the levels of eHSP70, which is associated with oxidative stress and low-grade
inflammation. Thus, it is reasonable to argue that HSP70 could determine the outcome of vascular
damage in this disease. Still, it is unknown if iHSP70 affects vascular Ca2+ signaling under
hyperglycemic conditions and if eHSP70 contributes to vascular functional and structural
alterations in diabetes. The central hypothesis of this project, formulated based on the literature
and my robust preliminary data, is that HSP70 plays a dual role in diabetes-induced vascular
dysfunction. This study is innovative because it will independently investigate the interplay
between iHSP70 and Ca2+ handling mechanisms leading to functional and structural changes
under hyperglycemia and by selectively targeting eHSP70 in a murine model of type 2 diabetes
to prevent these changes. I will combine a set of well-established in vitro, ex vivo, and in vivo
approaches, by using state-of-art techniques such as atomic force microcopy and
ultrasonography (Pulse Wave Velocity) to allow observations at macro, micro and nano scale.
Also, sex plays a crucial role in determining the tissue rate of production of HSP70; therefore, we
will use male and female animals. The experiments outlined in this study will address each specific
aim efficiently by utilizing the strengths of my laboratory. Moreover, network between biology and
engineering will be stablished by collaboration with a senior professor in Biomedical Engineering.
The PI has extensive experience in the field and will closely supervise the students. The outcome
of this research has an enormous potential to uncover target mechanisms to manage diabetic
vasculopathies while creating a multidisciplinary environment offering extensive research training
to undergraduate students. Our findings will have a broader impact by opening new research
avenues for other diseased states associated with vascular structural and functional changes.
热休克蛋白70在糖尿病诱导的血管功能障碍中的双重作用
项目成果
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Kenia Pedrosa Nunes其他文献
Kenia Pedrosa Nunes的其他文献
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