title: Serum from Varicose Patients Induces Senescence-Related Dysfunction of Vascular Endothelium Generating Local and Systemic Proinflammatory Conditions.
abstract: Although the role of endothelium in varicose vein development is indisputable, the effect of the pathology on biological properties of endothelial cells remains unclear. Here we examined if the presence of varicose veins affects senescence of endothelial cells (HUVECs) and, if so, what will be the local and systemic outcome of this effect. Experiments showed that HUVECs subjected to serum from varicose patients display improved proliferation, increased expression of senescence marker, SA-β-Gal, and increased generation of reactive oxygen species (ROS), as compared with serum from healthy donors. Both increased SA-β-Gal activity and ROS release were mediated by TGF-β1, the concentration of which in varicose serum was elevated and the activity of whichin vitrowas prevented using specific neutralizing antibody. Senescent HUVECs exposed to varicose serum generated increased amounts of ICAM-1, VCAM-1, P-selectin, uPA, PAI-1, and ET-1. Direct comparison of sera from varicose and healthy donors showed that pathological serum contained increased level of ICAM-1, VCAM-1, P-selectin, uPA, and ET-1. Calendar age of healthy subjects correlated positively with serum uPA and negatively with P-selectin. Age of varicose patients correlated positively with ICAM-1, VCAM-1, and ET-1. Collectively, our findings indicate that the presence of varicose veins causes a senescence-related dysfunction of vascular endothelium, which leads to the development of local and systemic proinflammatory environment.
authors.affiliation: Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str., 61-848 Poznań, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Mikuła-Pietrasik
authors.affiliation: Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str., 61-848 Poznań, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Uruski
authors.affiliation: Department of General and Vascular Surgery, Poznań University of Medical Sciences, Długa 1/2 Str., 61-848 Poznań, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Aniukiewicz
authors.affiliation: Department of Pathophysiology, Poznań University of Medical Sciences, Rokietnicka 8 Str., 60-806 Poznań, Poland.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Sosińska
authors.affiliation: Department of General and Vascular Surgery, Poznań University of Medical Sciences, Długa 1/2 Str., 61-848 Poznań, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Krasiński
authors.affiliation: Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str., 61-848 Poznań, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Tykarski
authors.affiliation: Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str., 61-848 Poznań, Poland.
authors.forename: Krzysztof
authors.identifier: 0000-0002-6066-5747
authors.initials: K
authors.lastname: Książek
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D014648:Varicose Veins / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D055815:Young Adult
chemical_list: D019332:Endothelin-1; C573420:ICAM1 protein, human; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1