Serum From Advanced Heart Failure Patients Promotes Angiogenic Sprouting and Affects the Notch Pathway in Human Endothelial Cells

Micaela Pannella, Cristiana Caliceti, Francesca Fortini, Giorgio Aquila, Francesco Vieceli Dalla Sega, Antonio Pannuti, Cinzia Fortini, Marco Bruno Morelli, Alessandro Fucili, Gloria Francolini, Rebecca Voltan, Paola Secchiero, Giovanni Dinelli, Emanuela Leoncini, Manuela Ferracin, Silvana Hrelia, Lucio Miele, Paola Rizzo

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2700-2710
Number of pages11
JournalJournal of Cellular Physiology
Issue number12
StatePublished - Dec 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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