Publication

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

Journal Paper/Review - Apr 4, 2019

Units
PubMed
Doi

Citation
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.
Type
Journal Paper/Review (English)
Journal
J Cell Mol Med 2019; 23
Publication Date
Apr 4, 2019
Issn Electronic
1582-4934
Pages
3916-3926
Brief description/objective

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.