grant
Endothelial TLR2/4 signaling in sex dimorphism of pathological angiogenesis and aging
Organization CLEVELAND CLINIC LERNER COM-CWRULocation CLEVELAND, UNITED STATESPosted 15 Dec 2025Deadline 30 Nov 2030
NIHUS FederalResearch GrantFY2026Active OxygenAgingApoptosisApoptosis PathwayAutoimmuneAutoregulationBiologicalBlood VesselsBody TissuesCell BodyCell Communication and SignalingCell Culture TechniquesCell FunctionCell PhysiologyCell ProcessCell SignalingCellsCellular FunctionCellular PhysiologyCellular ProcessChemicalsCodeCoding SystemCoupledDNA ContentDNA IndexDNA PloidyData SetDevelopmentDifferences between sexesDiffers between sexesDiseaseDisorderDysfunctionEndothelial CellsEndotheliumEnvironmental FactorEnvironmental Risk FactorExhibitsFemaleFemale HealthFour Core GenotypesFunctional disorderGene Expression MonitoringGene Expression Pattern AnalysisGene Expression ProfilingGenerationsGenesGeneticGonadal Steroid HormonesGonosomesHomeostasisHomolog of Drosophila TOLLHormonalHumanIRAKIRAK1IRAK1 geneImmuneImmunesImpairmentIn VitroInflammationInflammation MediatorsInflammatoryInflammatory ResponseInterleukin-1 Receptor-Associated Kinase 1Intracellular Communication and SignalingKO miceKnock-out MiceKnockout MiceLigandsLineage TracingMediatingMiceMice MammalsModelingModern ManMolecularMurineMusNull MouseOutcomeOxygen RadicalsPathologic AngiogenesisPathologic NeovascularizationPathological AngiogenesisPathological NeovascularizationPathologyPathway interactionsPatternPhenotypePhosphatidesPhospholipidsPhysiologic AngiogenesisPhysiologic NeovascularizationPhysiological AngiogenesisPhysiological HomeostasisPhysiological NeovascularizationPhysiopathologyPlayPloidiesPro-OxidantsProductionProgrammed Cell DeathProteinsProteomicsPublishingRNA SeqRNA sequencingRNAseqReactive Oxygen SpeciesReceptor ProteinResearchResearch SpecimenRoleSex ChromosomesSex DifferencesSex HormonesSex Steroid HormonesSexual differencesShapesSignal TransductionSignal Transduction SystemsSignalingSpecimenSubcellular ProcessTIL4TLR proteinTLR2TLR2 geneTLR2 receptorTLR4TLR4 geneTestingTherapeuticTissuesToll HomologueToll-Like Receptor 2Toll-Like Receptor Family GeneToll-like receptorsToll/Interleukin 1 Receptor-Like 4Toll/Interleukin 1 Receptor-Like 4 GeneToll/Interleukin 1 Receptor-Like Protein 4Transcript Expression AnalysesTranscript Expression AnalysisTransgenic MiceUpregulationVascular DiseasesVascular DisorderVascular remodelingVascularizationWomanWomen's HealthX ChromosomeXY femalesaberrant agingabnormal agingage associated chronic conditionage associated chronic diseaseage associated chronic disorderage associated chronic health conditionage associated chronic illnessage associated diseaseage associated disorderage associated impairmentage dependent diseaseage dependent disorderage dependent impairmentage related chronic conditionage related chronic diseaseage related chronic disorderage related chronic health conditionage related chronic illnessage related human diseaseage-related diseaseage-related disorderage-related impairmentanalyze gene expressionangiogenesisbiologicbiological signal transductionblood vessel disorderburden of chronic diseaseburden of chronic illnesscell culturecell culturescell lineage analysiscell lineage mappingcell lineage tracingcell lineage trackingcellular lineage mappingcellular lineage trackingchromosome complementcomparing females and malescomparing women and mencytokinedevelopmentaldysfunctional age related changedysfunctional agingenvironmental riskfemales compared to malesfemales compared with malesfemales versus malesfemales vs. malesgene expression analysisgene expression assaygonadal steroidsimpaired agingimprovedin vivoinflammatory mediatorinhibitorinjury responseinnate immune mechanismsinnovateinnovationinnovativeinsightmaladaptive agingmalemenmitochondrial dysfunctionmolecular recognitionmouse modelmurine modelnoveloxidationpathogenpathological age related changespathological agingpathophysiologypathwaypellepharmacologicreceptorreceptor expressionrecruitregenerate new tissueregenerate tissueregenerating damaged tissueregenerating tissueresponseresponse to injurysenescencesenescentsexsex based differencessex dimorphismsex steroidsex-dependent differencessex-related differencessex-specific differencessexual dimorphismsexually dimorphicsocial roletissue regenerationtissue regrowthtissue renewaltissue specific regenerationtoll-like receptor 4transcriptional profilingtranscriptome sequencingtranscriptomic sequencingvascularvascular dysfunctionvascular inflammationvasculopathywomen compared to menwomen compared with menwomen versus menwomen vs. men♀♂
Description preview
ABSTRACT
Numerous studies have demonstrated the "male-female health-survival paradox," where females exhibit a higher
burden of age-associated disorders yet live longer than males. This paradox arises from a greater burden of
chronic diseases in females, particularly those with a strong inflammatory or autoimmune component. A key
factor…
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