biostudies-literatureReventun PNHLBI NIH HHSe323000https://www.ebi.ac.uk/biostudies/studies/S-EPMC12823045biostudies-literatureUnknown46(3)<h4>Background</h4>Abnormal 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 <i>RAB5C</i> (RAS [rat sarcoma]-associated protein RAB5C). We hypothesized that RAB5C regulates VWF release from endothelial cells.<h4>Methods</h4>We 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 Arteriosclerosis, thrombosis, and vascular biologyRAB5C Increases Endothelial Release of VWF by Regulating Vesicle Trafficking.PMC12823045K08 HL166690R01 HL173974R01 HL164478R33 HL141791R01 HL139553R61 HL141791R01 HL126974R01 HL174778R01 HL105756Alcharani NReventun PArvanitis MGonzalez-Cucharero CSabater-Lleal MDelgado-Marin MMorrison ACOsburn WOLowenstein CJSmith NLWolberg ASViskadourou MToledano-Sanz PCohorts for Heart and Aging in Genomic Epidemiology Hemostasis Working GroupFoster DBde Vries PSfalseRAB5C Increases Endothelial Release of VWF by Regulating Vesicle Trafficking.<h4>Background</h4>Abnormal 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 <i>RAB5C</i> (RAS [rat sarcoma]-associated protein RAB5C). We hypothesized that RAB5C regulates VWF release from endothelial cells.<h4>Methods</h4>We 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 2026-01-01T00:00:00Z2026 Mar2026-07-16T21:26:55.616Z2026-07-10T03:14:57.288ZS-EPMC128230454153726310.1161/atvbaha.125.32300010.1161/ATVBAHA.125.323000