Publikation

SDF-1/CXCR4 signalling is involved in blood vessel growth and remodelling by intussusception

Wissenschaftlicher Artikel/Review - 04.04.2019

Bereiche
PubMed
DOI

Zitation
Dimova I, Karthik S, Makanya A, Hlushchuk R, Semela D, Volarevic V, Djonov V. SDF-1/CXCR4 signalling is involved in blood vessel growth and remodelling by intussusception. J Cell Mol Med 2019; 23:3916-3926.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
J Cell Mol Med 2019; 23
Veröffentlichungsdatum
04.04.2019
eISSN (Online)
1582-4934
Seiten
3916-3926
Kurzbeschreibung/Zielsetzung

The precise mechanisms of SDF-1 (CXCL12) in angiogenesis are not fully elucidated. Recently, we showed that Notch inhibition induces extensive intussusceptive angiogenesis by recruitment of mononuclear cells and it was associated with increased levels of SDF-1 and CXCR4. In the current study, we demonstrated SDF-1 expression in liver sinusoidal vessels of Notch1 knockout mice with regenerative hyperplasia by means of intussusception, but we did not detect any SDF-1 expression in wild-type mice with normal liver vessel structure. In addition, pharmacological inhibition of SDF-1/CXCR4 signalling by AMD3100 perturbs intussusceptive vascular growth and abolishes mononuclear cell recruitment in the chicken area vasculosa. In contrast, treatment with recombinant SDF-1 protein increased microvascular density by 34% through augmentation of pillar number compared to controls. The number of extravasating mononuclear cells was four times higher after SDF-1 application and two times less after blocking this pathway. Bone marrow-derived mononuclear cells (BMDC) were recruited to vessels in response to elevated expression of SDF-1 in endothelial cells. They participated in formation and stabilization of pillars. The current study is the first report to implicate SDF-1/CXCR4 signalling in intussusceptive angiogenesis and further highlights the stabilizing role of BMDC in the formation of pillars during vascular remodelling.