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
2015
Impaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease
Srivastava R, Zhang J, Go GW, Narayanan A, Nottoli TP, Mani A. Impaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease. Cell Reports 2015, 13: 746-759. PMID: 26489464, PMCID: PMC4626307, DOI: 10.1016/j.celrep.2015.09.028.Peer-Reviewed Original ResearchConceptsCoronary artery diseaseLRP6 activityArtery diseaseObstructive coronary artery diseaseHigh-fat dietVascular smooth muscle cell differentiationMuscle cell plasticitySmooth muscle cell differentiationAtherosclerotic burdenMedial hyperplasiaCarotid injuryArterial diseaseVascular obstructionNeointima formationTherapeutic targetWnt3a administrationIntact WntVSMC differentiationKnockout backgroundDiseaseMiceVessel wallNon-canonical WntCoreceptor LRP6Cell plasticity
2014
The Combined Hyperlipidemia Caused by Impaired Wnt-LRP6 Signaling Is Reversed by Wnt3a Rescue
Go GW, Srivastava R, Hernandez-Ono A, Gang G, Smith SB, Booth CJ, Ginsberg HN, Mani A. The Combined Hyperlipidemia Caused by Impaired Wnt-LRP6 Signaling Is Reversed by Wnt3a Rescue. Cell Metabolism 2014, 19: 209-220. PMID: 24506864, PMCID: PMC3920193, DOI: 10.1016/j.cmet.2013.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisCells, CulturedFatty LiverHepatocytesHyperlipidemiasLow Density Lipoprotein Receptor-Related Protein-6Mechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MiceModels, BiologicalMultiprotein ComplexesMutationNon-alcoholic Fatty Liver DiseaseTOR Serine-Threonine KinasesWnt3A ProteinConceptsHepatic de novo lipogenesisFatty liver diseaseElevated plasma LDLTreatment of hyperlipidemiaSp1-dependent activationCholesterol biosynthesisDe novo lipogenesisAtherogenic lipid disordersMolecular genetic basisLiver diseaseFatty liverLDL levelsPlasma lipidsTG levelsLipid disordersPlasma TGPlasma LDLNovo lipogenesisHyperlipidemiaCombined HyperlipidemiaGenetic basisWnt coreceptorNonconservative mutationsAltered expressionPrimary hepatocytes