title: Circulating cytokines present in the serum of peripheral arterial disease patients induce endothelial dysfunction.
abstract: Peripheral arterial disease (PAD) is a chronic condition caused by atherosclerosis and is a severe complication of type 2 diabetes (T2D). We hypothesised that chronic condition of arterial disease engenders inflammation and endothelial damage in response to circulating cytokines released in the blood stream of PAD patients. We explored the levels of circulating cytokines in PAD patients with and without diabetes by multiplex cytokine array compared with non-PAD controls. Serum from PAD patients with or without diabetes showed high levels of VEGF, IFN-gamma, TNF-alpha, MCP-1, and EGF. VEGF levels correlated with TNF-alpha and IFN-gamma, significantly. Endothelial cells (ECs) were exposed to the different altered cytokines to evaluate changes in cell growth, migration and tubule-like formation, displaying impairment on proliferation, migration and tubule formation. Our findings demonstrate that a set of cytokines is significantly increased in the serum of PAD patients. These cytokines act to induce endothelial dysfunction synergistically. VEGF strongly correlated with TNF-alpha and IFN-gamma, opening new therapeutic perspectives.
authors.affiliation: Department of General Pathology, Second University of Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Botti
authors.forename: C
authors.initials: C
authors.lastname: Maione
authors.forename: G
authors.initials: G
authors.lastname: Dogliotti
authors.forename: P
authors.initials: P
authors.lastname: Russo
authors.forename: G
authors.initials: G
authors.lastname: Signoriello
authors.forename: A M
authors.initials: AM
authors.lastname: Molinari
authors.forename: M M
authors.initials: MM
authors.lastname: Corsi
authors.forename: V
authors.initials: V
authors.lastname: Sica
authors.forename: G
authors.initials: G
authors.lastname: Cobellis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood* / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000209:etiology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004815:Epidermal Growth Factor; D007371:Interferon-gamma