2023
A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension
Gunawardhana K, Hong L, Rugira T, Uebbing S, Kucharczak J, Mehta S, Karunamuni D, Cabera-Mendoza B, Gandotra N, Scharfe C, Polimanti R, Noonan J, Mani A. A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension. Journal Of Clinical Investigation 2023, 133: e160036. PMID: 36602864, PMCID: PMC9927944, DOI: 10.1172/jci160036.Peer-Reviewed Original ResearchConceptsDevelopment of hypertensionParallel reporter assaysRenin inhibitor aliskirenNeural crest-derived cellsRenin-producing cellsSystems biology approachRNA-seq analysisCell-specific disruptionCrest-derived cellsSmooth muscle cellsMuscle cell proteinsSystemic hypertensionBlood pressureWT miceAntihypertensive drugsBiology approachSuper enhancersFine mappingWT littermatesThird intronMultiple GWASCollagen depositionMouse aortaReporter assaysFate mapping
2021
Wnt Signaling Cascades and Their Role in Coronary Artery Health and Disease
Weerackoon N, Gunawardhana KL, Mani A. Wnt Signaling Cascades and Their Role in Coronary Artery Health and Disease. Journal Of Cellular Signaling 2021, 2: 52-62. PMID: 33969358, PMCID: PMC8098721, DOI: 10.33696/signaling.2.035.Peer-Reviewed Original ResearchCoronary artery diseaseVascular smooth muscle cellsLow-density lipoproteinPlaque erosionDisease processWnt pathwayAdult cardiovascular diseaseDistinct disease processesSmooth muscle proliferationType 2 diabetesCause of deathMajor congenital defectsModified low-density lipoproteinSmooth muscle cellsWnt/β-catenin signalingCoronary artery healthCanonical Wnt/β-catenin signalingAggregation of monocytesActivation of WntΒ-catenin signalingArtery diseaseEndothelial cell defectsEndothelial dysfunctionWnt/CaVascular inflammation
2020
The role of Wnt signalling in development of coronary artery disease and its risk factors
Liu Y, Neogi A, Mani A. The role of Wnt signalling in development of coronary artery disease and its risk factors. Open Biology 2020, 10: 200128. PMID: 33081636, PMCID: PMC7653355, DOI: 10.1098/rsob.200128.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBiomarkersCarrier ProteinsCell DifferentiationCell MovementCoronary Artery DiseaseDisease SusceptibilityEndotheliumGene Expression RegulationHumansLipid MetabolismMacrophage ActivationMacrophagesMyocytes, Smooth MuscleProtein BindingRisk FactorsWnt ProteinsWnt Signaling PathwayConceptsCoronary artery diseaseArtery diseaseRole of WntVascular smooth muscle cellsEndothelial cell dysfunctionReduced blood flowLow-density lipoproteinModified low-density lipoproteinWnt pathwaySmooth muscle cellsNon-canonical Wnt/CaAggregation of monocytesTissue-resident macrophagesChest painEndothelial dysfunctionWnt/CaHeart failureLuminal narrowingCascade of eventsPathophysiological mechanismsMyocardial infarctionRisk factorsHeart diseaseCell dysfunctionInflammatory reaction
2018
TCF7L2 (Transcription Factor 7-Like 2) Regulation of GATA6 (GATA-Binding Protein 6)-Dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia
Srivastava R, Rolyan H, Xie Y, Li N, Bhat N, Hong L, Esteghamat F, Adeniran A, Geirsson A, Zhang J, Ge G, Nobrega M, Martin KA, Mani A. TCF7L2 (Transcription Factor 7-Like 2) Regulation of GATA6 (GATA-Binding Protein 6)-Dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia. Arteriosclerosis Thrombosis And Vascular Biology 2018, 39: 250-262. PMID: 30567484, PMCID: PMC6365015, DOI: 10.1161/atvbaha.118.311830.Peer-Reviewed Original ResearchConceptsInjury-induced intimal hyperplasiaIntimal hyperplasiaObstructive coronary artery diseaseVascular smooth muscle cell dedifferentiationSmooth muscle cell dedifferentiationVascular Smooth Muscle Cell PlasticityLRP6 mutant miceOverexpression of TCF7L2Coronary artery diseaseVascular smooth muscle cellsMultiple mouse modelsMuscle cell dedifferentiationWild-type littermatesSmooth muscle cellsRole of TCF7L2Smooth Muscle Cell PlasticityVascular smooth muscle cell differentiationMuscle cell plasticitySmooth muscle cell differentiationArtery diseaseSM-MHCMouse modelCell cycle inhibitorsHaploinsufficient miceHyperplasia
2016
Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus
Li N, Subrahmanyan L, Smith E, Yu X, Zaidi S, Choi M, Mane S, Nelson-Williams C, Behjati M, Kazemi M, Hashemi M, Fathzadeh M, Narayanan A, Tian L, Montazeri F, Mani M, Begleiter ML, Coon BG, Lynch HT, Olson EN, Zhao H, Ruland J, Lifton RP, Mani A. Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus. American Journal Of Human Genetics 2016, 98: 1082-1091. PMID: 27181681, PMCID: PMC4908195, DOI: 10.1016/j.ajhg.2016.03.022.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsHistone methyl transferase activityWhole-exome sequencingGenome-wide linkage analysisWild-type proteinPatent ductus arteriosusMethyl transferase activityEpigenetic regulationLoss of functionTranscriptional suppressorNuclear proteinsPremature differentiationMethyltransferase activityCommon congenital heart defectUndifferentiated stageIndependent mutationsDuctus arteriosusLinkage analysisIntracellular redistributionNumber of VSMCsPRDM6Smooth muscle cellsProteinMutationsDisease mechanisms