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Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells
Author(s) -
Pannella Micaela,
Caliceti Cristiana,
Fortini Francesca,
Aquila Giorgio,
Vieceli Dalla Sega Francesco,
Pannuti Antonio,
Fortini Cinzia,
Morelli Marco Bruno,
Fucili Alessandro,
Francolini Gloria,
Voltan Rebecca,
Secchiero Paola,
Dinelli Giovanni,
Leoncini Emanuela,
Ferracin Manuela,
Hrelia Silvana,
Miele Lucio,
Rizzo Paola
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25373
Subject(s) - notch signaling pathway , microbiology and biotechnology , sprouting , angiogenesis , heart failure , biology , medicine , cancer research , chemistry , signal transduction , botany
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.