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Role of Oral Microbiota on Vascular Function

Role of Oral Microbiota on Vascular Function
口腔微生物群对血管功能的作用
批准号:
10628184
负责人:
PANDU R GANGULA
金额:
$14.55万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-09-01 至 2027-06-30
关键词:
AnabolismAnimal ModelAntioxidantsAortaAttenuatedBiological AvailabilityBlood VesselsCardiovascular DiseasesCardiovascular systemCell SurvivalChronicChronic DiseaseCollaborationsCommunicable DiseasesComplexCoronary heart diseaseCyclic GMPDataDevelopmentDiabetes MellitusDietary SupplementationDimerizationDisease modelEarly DiagnosisEndothelial CellsEnzymesErythroidEventExhibitsFemaleForsythiaFusobacterium nucleatumGoalsGram-Negative BacteriaHumanHyperglycemiaHypertensionImmune signalingImpairmentIn VitroIndividualInfectionInflammationInflammatoryInflammatory ResponseLaboratoriesMeasuresMediatingModelingMolecularMusMuscle relaxation phaseMyocardial InfarctionNOS3 geneNitric OxideNon-Insulin-Dependent Diabetes MellitusNuclearOral cavityOxidative StressPathogenesisPathologyPathway interactionsPeriodontal DiseasesPeriodontal InfectionPeriodontitisPersonsPlayPorphyromonas gingivalisProtein KinasePublicationsReactive Oxygen SpeciesRelaxationReportingResearchResearch PersonnelResistanceRiskRodentRodent ModelRoleSignal TransductionSoluble Guanylate CyclaseStrokeSupplementationTestingTexasTimeTreponema denticolaVascular DiseasesVascular EndotheliumVascular Smooth Muscleantioxidant enzymecardiovascular risk factorcofactorcollegecytokinediabeticdiabetic patienteffective interventionendothelial dysfunctionenzyme activityenzyme biosynthesisexperienceimprovedin vivomalenon-diabeticnoveloral infectionoral microbial communityoxidationpathogenperiodontopathogenprotein expressionsepiapterintetrahydrobiopterinvascular endothelial dysfunction

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中文摘要
翻译
糖尿病(DM)和牙周病(PD)是一种复杂的慢性疾病
英文摘要
Diabetes Mellitus (DM) and periodontal diseases (PD) are complex chronic diseases with an established bidirectional relationship. People with PD have two to three times the risk of having a heart attack, stroke, or serious cardiovascular complications. PD in individuals with diabetes contributes to aggravated inflammatory response leading to vascular disease (VD). Our group has previously shown that PD increases coronary heart disease in diabetic patients. Nitric oxide (NO) mediated endothelial dysfunction is the initial step in the development of VD. Reduced NO bioavailability due to the lack of tetrahydrobiopterin [BH4, a cofactor for endothelial nitric oxide synthase (eNOS)], resulting in eNOS uncoupling, increases oxidative stress/inflammation, impaired vascular smooth muscle relaxation and contributes to CV pathologies in diabetic patients and rodent models of diabetes. Our previous studies demonstrated that chronic periodontal infection reduced circulatory BH4 and NO levels and this reduction correlated with impaired immune signaling. In addition, decreased levels of nuclear factor (erythroid-derived-2)-like 2 (Nrf2)-dependent antioxidants and increased levels of reactive oxygen species (ROS) also play a critical role in hypertension and vascular function. We recently reported that primary human aortic endothelial cells (pHAECs) infected with Porphyromonas gingivalis (Pg, a major periodontal pathogen), exhibited reduced cell viability, elevated pro-inflammatory cytokines, reduced Nrf2/eNOS and BH4 biosynthesis. In addition, our in-vivo rodent studies demonstrate that chronic polybacterial periodontal infection [Pg, Treponema denticola (Td), and Fusobacterium nucleatum (Fn), a model of PD in humans] reduced the protein expression of Nrf2/BH4/nNOS in resistance blood vessels of the infected mice. However, the specific mechanisms that contribute to aggravated inflammation and oxidative stress during PD and diabetes leading to endothelial dysfunction is completely unknown. Our central hypothesis is that BH4 regulates NO-mediated vascular function, which is greatly impaired in diabetic PD compared to diabetes or PD alone. The specific aims are,1: To determine whether hyperglycemia (HG) aggravates PD-induced impairment in BH4/NOS and NO downstream signaling in pHAECs. 2: To investigate whether increased endogenous BH4 biosynthesis suppresses PD/T2DM induced inflammation, oxidative stress and restores eNOS activity, NO synthesis, and NO mediated vascular relaxation. The proposed studies will be the first to determine the role of periodontal pathogens in NO-mediated vascular function in T2DM animal models. The research outlined in these aims has translational relevance, as it has the potential to identify novel treatment; options for PD/T2DM induced VD.
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Multidisciplinary Practice-Based Research Training in Meharry Medical College, School of Dentistry
  • 批准号:
    10754751
  • 项目类别:
  • 资助金额:
    $58.99万
  • 财政年份:
    2023
  • 负责人:
    PANDU R GANGULA
  • 依托单位:
ROLE OF NRF2 IN NITRERGIC MEDIAITED STOMACH MOTILITY
  • 批准号:
    10004085
  • 项目类别:
  • 资助金额:
    $36.38万
  • 财政年份:
    2017
  • 负责人:
    PANDU R GANGULA
  • 依托单位:
ROLE OF NRF2 IN NITRERGIC MEDIAITED STOMACH MOTILITY
  • 批准号:
    9767832
  • 项目类别:
  • 资助金额:
    $36.38万
  • 财政年份:
    2017
  • 负责人:
    PANDU R GANGULA
  • 依托单位:
ROLE OF NRF2 IN NITRERGIC MEDIAITED STOMACH MOTILITY
  • 批准号:
    9209154
  • 项目类别:
  • 资助金额:
    $35.69万
  • 财政年份:
    2017
  • 负责人:
    PANDU R GANGULA
  • 依托单位:
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