2021
Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis
Price NL, Zhang X, Fernández-Tussy P, Singh AK, Burnap SA, Rotllan N, Goedeke L, Sun J, Canfrán-Duque A, Aryal B, Mayr M, Suárez Y, Fernández-Hernando C. Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2006478118. PMID: 33495342, PMCID: PMC7865172, DOI: 10.1073/pnas.2006478118.Peer-Reviewed Original ResearchConceptsMiR-33 deficiencyHDL-C levelsMiR-33Body weightAtherosclerotic plaque sizeAtherosclerotic plaque burdenDevelopment of fibrosisCholesterol transport capacityCholesterol transporter ABCA1High-density lipoprotein biogenesisSREBP2 transcription factorKnockout mouse modelConditional knockout mouse modelPlaque burdenCardiometabolic diseasesChow dietLiver functionMetabolic dysfunctionHDL metabolismHyperlipidemic conditionsMouse modelGlucose homeostasisCholesterol effluxLipid metabolismObesity
2019
Integrin α5β1 regulates PP2A complex assembly through PDE4D in atherosclerosis
Yun S, Hu R, Schwaemmle ME, Scherer AN, Zhuang Z, Koleske AJ, Pallas DC, Schwartz MA. Integrin α5β1 regulates PP2A complex assembly through PDE4D in atherosclerosis. Journal Of Clinical Investigation 2019, 129: 4863-4874. PMID: 31408443, PMCID: PMC6819111, DOI: 10.1172/jci127692.Peer-Reviewed Original ResearchConceptsPP2A regulatory subunit B55αTranscription factor YAPActive PDEComplex assemblyAdapter rolePDE4D5B55αIntegrin α5EC phenotypeCell functionInflammatory signalingAthero-prone regionsActivationComplexesPP2AInflammatory activationWidespread consequencesDephosphorylationProteomicsVascular remodelingPlaque sizeAtherosclerotic plaque sizeSignalingYAPRegulates
2018
Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis
Budatha M, Zhang J, Zhuang ZW, Yun S, Dahlman JE, Anderson DG, Schwartz MA. Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis. Journal Of The American Heart Association 2018, 7: e007501. PMID: 29382667, PMCID: PMC5850249, DOI: 10.1161/jaha.117.007501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesAtherosclerosisCyclic Nucleotide Phosphodiesterases, Type 4Disease Models, AnimalExtracellular MatrixFibronectinsFibrosisGenetic Predisposition to DiseaseHindlimbInflammation MediatorsIntegrin alpha2Integrin alpha5IschemiaLeukocytesMaleMatrix MetalloproteinasesMice, Inbred C57BLMice, Knockout, ApoEMuscle, SkeletalNeovascularization, PhysiologicNF-kappa BPhenotypePlaque, AtheroscleroticSignal TransductionVascular RemodelingConceptsEndothelial inflammatory activationAtherosclerotic plaque sizeInflammatory activationPlaque stabilityVascular remodelingEndothelial NF-κB activationSmooth muscle cell contentPlaque sizeFemoral artery ligationMuscle cell contentTreatment of atherosclerosisInflammatory gene expressionPotential therapeutic targetFibrous cap thicknessNF-κB activationSmaller atherosclerotic plaquesArtery ligationAortic rootHindlimb ischemiaCompensatory remodelingAtherosclerotic plaquesTherapeutic targetLeukocyte contentMetalloproteinase expressionEndothelial basement membrane
2017
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice
Fuster JJ, MacLauchlan S, Zuriaga MA, Polackal MN, Ostriker AC, Chakraborty R, Wu CL, Sano S, Muralidharan S, Rius C, Vuong J, Jacob S, Muralidhar V, Robertson AA, Cooper MA, Andrés V, Hirschi KK, Martin KA, Walsh K. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 2017, 355: 842-847. PMID: 28104796, PMCID: PMC5542057, DOI: 10.1126/science.aag1381.Peer-Reviewed Original ResearchConceptsTET2-deficient cellsLow-density lipoprotein receptor-deficient miceLipoprotein receptor-deficient miceClonal hematopoiesisBlood cellsAtherosclerotic cardiovascular diseaseAtherosclerotic plaque sizeReceptor-deficient miceBone marrow reconstitutionInterleukin-1β secretionMutant blood cellsAtherosclerosis developmentNLRP3 inhibitorAtheroprotective activityCardiovascular diseaseMarrow reconstitutionChimeric micePlaque sizeClonal expansionMiceMarked increaseCausal roleTET2 deficiencySomatic mutationsHematopoietic cells
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