2023
Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice
Lee S, Schleer H, Park H, Jang E, Boyer M, Tao B, Gamez-Mendez A, Singh A, Folta-Stogniew E, Zhang X, Qin L, Xiao X, Xu L, Zhang J, Hu X, Pashos E, Tellides G, Shaul P, Lee W, Fernandez-Hernando C, Eichmann A, Sessa W. Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice. Nature Cardiovascular Research 2023, 2: 438-448. PMID: 39196046, PMCID: PMC11358031, DOI: 10.1038/s44161-023-00266-2.Peer-Reviewed Original ResearchLDL transcytosisLDL receptor knockout miceReceptor knockout miceAtherosclerotic cardiovascular diseaseLow-density lipoprotein accumulationHigh-fat dietPromising therapeutic strategyTherapeutic neutralizationMacrophage infiltrationTriglyceride levelsLDL entryCardiovascular diseaseSelective monoclonal antibodiesLipoprotein accumulationTherapeutic strategiesKnockout micePlaque formationAtherosclerosis initiationType 1Genetic deletionArterial wallMonoclonal antibodiesEndothelial cellsLDL accumulationMice
2020
BMP-9 and LDL crosstalk regulates ALK-1 endocytosis and LDL transcytosis in endothelial cells
Tao B, Kraehling JR, Ghaffari S, Ramirez C, Lee S, Fowler JW, Lee WL, Fernandez-Hernando C, Eichmann A, Sessa WC. BMP-9 and LDL crosstalk regulates ALK-1 endocytosis and LDL transcytosis in endothelial cells. Journal Of Biological Chemistry 2020, 295: 18179-18188. PMID: 33097593, PMCID: PMC7939458, DOI: 10.1074/jbc.ra120.015680.Peer-Reviewed Original ResearchConceptsBone morphogenetic protein 9Dynamin 2Caveolin-1LDL transcytosisGene expressionActivin-like kinase 1Endothelial cellsEndothelial cell quiescenceCell surface levelsSmad1/5 phosphorylationExtensive endocytosisUnbiased screenProtein 9Cell quiescenceKinase 1ALK-1BMP-9 levelsEssential roleEndocytosisEndothelial homeostasisHeavy chainSignalingInternalizationTranscytosisCells
2016
Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells
Kraehling JR, Chidlow JH, Rajagopal C, Sugiyama MG, Fowler JW, Lee MY, Zhang X, Ramírez CM, Park EJ, Tao B, Chen K, Kuruvilla L, Larriveé B, Folta-Stogniew E, Ola R, Rotllan N, Zhou W, Nagle MW, Herz J, Williams KJ, Eichmann A, Lee WL, Fernández-Hernando C, Sessa WC. Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells. Nature Communications 2016, 7: 13516. PMID: 27869117, PMCID: PMC5121336, DOI: 10.1038/ncomms13516.Peer-Reviewed Original ResearchConceptsActivin-like kinase 1Wide RNAi screenGWA data setsLDL uptakeEndothelial cellsIdentification of pathwaysLDL receptorRNAi screenEndocytic pathwayLysosomal degradationKinase 1LDL transcytosisPhysiological roleGenetic ablationUptake of LDLPathwayFunctional LDL receptorsCellsLow affinityTranscytosisUptakeALK1Unique opportunityAortic endotheliumAnimals