ArticleArteriosclerosis, thrombosis, and vascular biology2026
RAB5C Increases Endothelial Release of VWF by Regulating Vesicle Trafficking.
Paula Reventun, Pablo Toledano-Sanz, Maria Delgado-Marin, Maria Viskadourou, D Brian Foster, Paul S de Vries, Maria Sabater-Lleal, Nunzio Alcharani, Claudia Gonzalez-Cucharero, William O Osburn and 6 more
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In one paragraphArticle in Arteriosclerosis, thrombosis, and vascular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
16 authors.
Paula ReventunDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (P.R., P.T.-S., M.D.-M., M.V., D.B.F., N.A., C.G.-C., W.O.O., M.A.).ORCID 0000-0002-6221-8780 Pablo Toledano-SanzDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (P.R., P.T.-S., M.D.-M., M.V., D.B.F., N.A., C.G.-C., W.O.O., M.A.).ORCID 0000-0002-8347-2227 Maria Delgado-MarinDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (P.R., P.T.-S., M.D.-M., M.V., D.B.F., N.A., C.G.-C., W.O.O., M.A.).ORCID 0000-0002-3078-7321 Maria ViskadourouDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (P.R., P.T.-S., M.D.-M., M.V., D.B.F., N.A., C.G.-C., W.O.O., M.A.).ORCID 0009-0004-3883-8471 D Brian FosterDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (P.R., P.T.-S., M.D.-M., M.V., D.B.F., N.A., C.G.-C., W.O.O., M.A.).ORCID 0000-0002-9290-9590 Paul S de VriesDepartment of Epidemiology, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston (P.S.d.V., A.C.M.).ORCID 0000-0003-0964-0111 Maria Sabater-LlealUnit of Genomics of Complex Disease, Institut de Recerca Sant Pau (IR-SANT PAU), Barcelona, Spain (M.S.-L.).ORCID 0000-0002-0128-379X Nunzio AlcharaniDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (P.R., P.T.-S., M.D.-M., M.V., D.B.F., N.A., C.G.-C., W.O.O., M.A.).ORCID 0000-0002-9477-7712 Claudia Gonzalez-CuchareroDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (P.R., P.T.-S., M.D.-M., M.V., D.B.F., N.A., C.G.-C., W.O.O., M.A.).
William O OsburnDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (P.R., P.T.-S., M.D.-M., M.V., D.B.F., N.A., C.G.-C., W.O.O., M.A.).ORCID 0000-0002-7472-3805 Alanna C MorrisonDepartment of Epidemiology, Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston (P.S.d.V., A.C.M.).ORCID 0000-0001-6381-4296 Alisa S WolbergDepartment of Pathology and Laboratory Medicine and UNC Blood Research Center, The University of North Carolina at Chapel Hill (A.S.W.).ORCID 0000-0002-2845-2303 Marios ArvanitisDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD (P.R., P.T.-S., M.D.-M., M.V., D.B.F., N.A., C.G.-C., W.O.O., M.A.).ORCID 0000-0001-8046-6123 Cohorts for Heart and Aging in Genomic Epidemiology Hemostasis Working Group
Funding
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MAnalysis of Whole Genome Sequence and Hemostasis PhenotypesR01HL139553 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI PAUL STEFAN DE VRIES, Alanna C Morrison · 2018 to 2026
$5.0MFibrinogen and Factor XIII in Venous ThrombosisR01HL126974 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Alisa S. Wolberg · 2016 to 2026
$4.4MRetinoid Metabolism in the Adult Heart and Heart FailureR01HL164478 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI D Brian Foster, MAUREEN A KANE · 2023 to 2026
$2.8MBCOR Regulation of Venous ThromboembolismR01HL174778 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI CHARLES J LOWENSTEIN, William Owen Osburn · 2024 to 2026
$2.0MModel system of oral contraceptive-induced VTE: integrating genomic, transcriptomic, and proteomic discovery with functional biologyR33HL141791 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI LOWENSTEIN, CHARLES J, SMITH, NICHOLAS L · 2020 to 2022
$2.0MInterdisciplinary approach to elucidate modifiers of bleeding phenotype in factor XI deficiencyR01HL173974 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Karin Leiderman, Alisa S. Wolberg · 2024 to 2026
$1.8MModel system of oral contraceptive-induced VTE: integrating genomic, transcriptomic, and proteomic discovery with functional biologyR61HL141791 · NHLBI · UNIVERSITY OF ROCHESTER · PI LOWENSTEIN, CHARLES J, SMITH, NICHOLAS L · 2018 to 2019
$1.4MFrom genotype to phenotype in a GWAS locus: the role of REST in atherosclerosisK08HL166690 · NHLBI · OHIO STATE UNIVERSITY · PI Marios Arvanitis · 2023 to 2026
$681kAmerican Heart Association-American Stroke Association 23POST1021300NHLBI NIH HHS K08 HL166690NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL126974NHLBI NIH HHS R01 HL139553NHLBI NIH HHS R01 HL164478NHLBI NIH HHS R01 HL173974NHLBI NIH HHS R01 HL174778NHLBI NIH HHS R33 HL141791NHLBI NIH HHS R61 HL141791
6 · The paper itselfAbstract
backgroundAbnormal levels of VWF (von Willebrand Factor) are a risk factor for venous thromboembolism (VTE) and bleeding. Genome-wide association studies for VWF have identified novel candidate genes that may regulate VWF levels in humans, including
methodsWe studied the effect of RAB5C on vesicle trafficking in human endothelial cells. We performed CRISPR (clustered regularly interspaced short palindromic repeats) interference targeting 2 genetic variants linked to altered VWF levels and evaluated RAB5C expression by reverse transcription-quantitative polymerase chain reaction. We silenced RAB5C or overexpressed RAB5C wild-type, constitutive active or dominant negative; and then, we measured VWF exocytosis from human umbilical vein endothelial cells to the media by ELISA. We performed proximity labeling and mass spectrometry to identify intracellular signaling pathways mediating the effects of RAB5C on VWF exocytosis.
resultsWe found that 2 genetic variants (rs9915255 and rs9912088 identified by genome-wide association studies for VWF levels) regulate
conclusionsTaken together, our data demonstrate that RAB5C regulates VWF release in part through SNAP29 control of vesicle trafficking in endothelial cells. These findings validate genetic epidemiology data linking RAB5C to VWF levels in humans and provide new insights into the molecular mechanisms regulating VWF exocytosis.
Indexed as
endothelial cellsgenome-wide association studythrombosisvenous thromboembolismvon Willebrand Factor
Identifiers
PMID41537263
PMCPMC12823045
What Socratic holds
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