title: Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells.
abstract: It is unknown whether components present in heart failure (HF) patients' serum provide an angiogenic stimulus. We sought to determine whether serum from HF patients affects angiogenesis and its major modulator, the Notch pathway, in human umbilical vein endothelial cells (HUVECs). In cells treated with serum from healthy subjects or from patients at different HF stage we determined: (1) Sprouting angiogenesis, by measuring cells network (closed tubes) in collagen gel. (2) Protein levels of Notch receptors 1, 2, 4, and ligands Jagged1, Delta-like4. We found a higher number of closed tubes in HUVECs treated with advanced HF patients serum in comparison with cells treated with serum from mild HF patients or controls. Furthermore, as indicated by the reduction of the active form of Notch4 (N4IC) and of Jagged1, advanced HF patients serum inhibited Notch signalling in HUVECs in comparison with mild HF patients' serum and controls. The circulating levels of NT-proBNP (N-terminal of the pro-hormone brain natriuretic peptide), a marker for the detection and evalutation of HF, were positively correlated with the number of closed tubes (r = 0.485) and negatively with Notch4IC and Jagged1 levels in sera-treated cells (r = -0.526 and r = -0.604, respectively). In conclusion, we found that sera from advanced HF patients promote sprouting angiogenesis and dysregulate Notch signaling in HUVECs. Our study provides in vitro evidence of an angiogenic stimulus arising during HF progression and suggests a role for the Notch pathway in it. J. Cell. Physiol. 231: 2700-2710, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Micaela
authors.initials: M
authors.lastname: Pannella
authors.affiliation: Department of Chemistry "G. Ciamician", University of Bologna, Bologna, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Caliceti
authors.affiliation: Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fortini
authors.affiliation: Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Aquila
authors.affiliation: Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Vieceli Dalla Sega
authors.affiliation: Stanley Scott Cancer Center, Louisiana State University Health Sciences Center and Louisiana Cancer Research Consortium, New Orleans, Louisiana.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pannuti
authors.affiliation: Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Fortini
authors.affiliation: Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Marco Bruno
authors.initials: MB
authors.lastname: Morelli
authors.affiliation: University Hospital of Ferrara, Ferrara, Italy.|Maria Cecilia Hospital, GVM Care & Research, E.S. Health Science Foundation, Cotignola, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fucili
authors.affiliation: Cardiovascular Research Center, Salvatore Maugeri Foundation IRCCS, Lumezzane, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Francolini
authors.affiliation: Department of Morphology, Surgery, and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Voltan
authors.affiliation: Department of Morphology, Surgery, and Experimental Medicine, University of Ferrara, Ferrara, Italy.|Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Secchiero
authors.affiliation: Department of Agricultural Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Dinelli
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Leoncini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Hrelia
authors.affiliation: Stanley Scott Cancer Center, Louisiana State University Health Sciences Center and Louisiana Cancer Research Consortium, New Orleans, Louisiana.
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele
authors.affiliation: Department of Morphology, Surgery, and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rizzo
mesh_terms: D000368:Aged; D003094:Collagen / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D005260:Female; D005782:Gels / Q000494:pharmacology; D006333:Heart Failure / Q000097:blood*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051880:Receptors, Notch / Q000378:metabolism*; D044967:Serum / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D005782:Gels; D051880:Receptors, Notch; D003094:Collagen