2023
The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques
Kabir I, Zhang X, Dave J, Chakraborty R, Qu R, Chandran R, Ntokou A, Gallardo-Vara E, Aryal B, Rotllan N, Garcia-Milian R, Hwa J, Kluger Y, Martin K, Fernández-Hernando C, Greif D. The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques. Nature Aging 2023, 3: 64-81. PMID: 36743663, PMCID: PMC9894379, DOI: 10.1038/s43587-022-00342-5.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsAtherosclerosisBone MarrowHumansIntegrin beta3MiceMuscle, SmoothMyocytes, Smooth MusclePlaque, AtheroscleroticConceptsAtherosclerotic plaquesBone marrowSmooth muscle-derived cellsSMC progenitorsAtherosclerotic plaque cellsSmooth muscle cell progenitorsPredominant risk factorCause of deathNovel therapeutic strategiesTNF receptor 1Muscle-derived cellsAged bone marrowAged BMEffect of agePlaque burdenAged miceRisk factorsTumor necrosisTherapeutic strategiesPlaque cellsMyeloid cellsReceptor 1Integrin β3Cell progenitorsAtherosclerosis
2019
CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation
Esteghamat F, Broughton JS, Smith E, Cardone R, Tyagi T, Guerra M, Szabó A, Ugwu N, Mani MV, Azari B, Kayingo G, Chung S, Fathzadeh M, Weiss E, Bender J, Mane S, Lifton RP, Adeniran A, Nathanson MH, Gorelick FS, Hwa J, Sahin-Tóth M, Belfort-DeAguiar R, Kibbey RG, Mani A. CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation. Nature Genetics 2019, 51: 1233-1243. PMID: 31358993, PMCID: PMC6675645, DOI: 10.1038/s41588-019-0470-3.Peer-Reviewed Original ResearchConceptsEarly-onset atherosclerosisMetabolic syndromeMetabolic syndrome traitsWhole-exome sequence analysisAttractive therapeutic targetPlatelet hyperactivationInsulin levelsPlasma insulinPlasma levelsInsulin sensitivityInsulin secretionTherapeutic targetPlatelet activationDisease mechanismsSyndrome traitsAtherosclerosisFunction mutationsSyndromeNovel lossInsulinMutationsSecretion
2013
Ten-Eleven Translocation-2 (TET2) Is a Master Regulator of Smooth Muscle Cell Plasticity
Liu R, Jin Y, Tang WH, Qin L, Zhang X, Tellides G, Hwa J, Yu J, Martin KA. Ten-Eleven Translocation-2 (TET2) Is a Master Regulator of Smooth Muscle Cell Plasticity. Circulation 2013, 128: 2047-2057. PMID: 24077167, PMCID: PMC3899790, DOI: 10.1161/circulationaha.113.002887.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCell DifferentiationCells, CulturedDioxygenasesDNA-Binding ProteinsEpigenesis, GeneticHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNuclear ProteinsPromoter Regions, GeneticProto-Oncogene ProteinsTrans-ActivatorsWound HealingConceptsTen-Eleven Translocation-2SMC differentiationTET2 knockdownSmooth muscle cellsGene expressionTranslocation 2Smooth Muscle Cell PlasticityMaster epigenetic regulatorSMC gene expressionContractile gene expressionMuscle cell plasticityDedifferentiated smooth muscle cellsTET2 overexpressionContractile smooth muscle cellsHuman smooth muscle cellsChromatin accessibilityEpigenetic landscapeSMC plasticityChromatin immunoprecipitationEpigenetic regulatorsEpigenetic mechanismsCell plasticityMaster regulatorSMC phenotypeTranscriptional upregulation