2023
Disturbed flow increases endothelial inflammation and permeability via a Frizzled-4-β-catenin-dependent pathway
Rickman M, Ghim M, Pang K, von Huelsen Rocha A, Drudi E, Sureda-Vives M, Ayoub N, Tajadura-Ortega V, George S, Weinberg P, Warboys C. Disturbed flow increases endothelial inflammation and permeability via a Frizzled-4-β-catenin-dependent pathway. Journal Of Cell Science 2023, 136: jcs260449. PMID: 36846872, PMCID: PMC10112981, DOI: 10.1242/jcs.260449.Peer-Reviewed Original ResearchConceptsEndothelial dysfunctionEndothelial cellsFrizzled-4Β-cateninCultured human aortic endothelial cellsR-spondinsHuman aortic endothelial cellsPro-inflammatory genesEndothelial paracellular permeabilityDisturbed flowAortic endothelial cellsCultured endothelial cellsRole of WntEndothelial inflammationAortic archEarly atherogenesisCanonical Wnt pathwayDysfunctionReduced expressionWnt5a signalingParacellular permeabilityWnt pathwayInhibitionKnockdownExpression
2022
Shear-mediated ALK5 expression regulates endothelial activation
Pang K, Ghim M, Sarathchandra P, Warboys C, Yacoub M, Chester A, Weinberg P. Shear-mediated ALK5 expression regulates endothelial activation. Biochemical And Biophysical Research Communications 2022, 642: 90-96. PMID: 36566567, DOI: 10.1016/j.bbrc.2022.12.058.Peer-Reviewed Original ResearchConceptsBlood flowCalcific aortic valve diseaseAortic valve diseaseHuman umbilical vein endothelial cell monolayersEndothelial-leukocyte adhesionALK5 kinase activityCardiovascular disease pathologyPotential therapeutic targetAortic valve tissueEndothelial dysfunctionValve diseaseALK5 expressionEndothelial activationFurther mechanistic investigationsEndothelial cell monolayersPorcine aortic valve tissuePathophysiological changesOvert diseaseAortic sidePathological changesTherapeutic targetVentricular sideLeukocyte adhesionMonocyte adhesionSmad2 phosphorylation
2017
Visualization of three pathways for macromolecule transport across cultured endothelium and their modification by flow
Ghim M, Alpresa P, Yang S, Braakman S, Gray S, Sherwin S, van Reeuwijk M, Weinberg P. Visualization of three pathways for macromolecule transport across cultured endothelium and their modification by flow. AJP Heart And Circulatory Physiology 2017, 313: h959-h973. PMID: 28754719, PMCID: PMC5792200, DOI: 10.1152/ajpheart.00218.2017.Peer-Reviewed Original ResearchConceptsShear stressDifferent flow profilesType of flowTransverse stressesNumerical simulationsFlow profileFluid mechanical forcesShear profileShear vectorSolute transportTwo-pore theoryStatic conditionsFlowMacromolecule transportMechanical forcesTransportStressMicrovessel wallShearOrbital shakerStress metricsLong axisTracer distributionSimulations