Role of Notch, SDF-1 and Mononuclear Cells Recruitment in Angiogenesis

Abstract

Intussusceptive angiogenesis (IA) known also as splitting angiogenesis is a recently described mechanism of vascular growth alternative to sprouting. It plays an essential role in the vascular remodeling and adaptation of vessels during normal and pathological angiogenesis. It is an "escape" mechanism during and after irradiation and anti-VEGF therapy, both inducing angiogenic switch from sprouting to IA by formation of multiple transluminal tissue pillars. Our recently published data revealed the significant induction of IA after inhibition of Notch signaling associated with an increased capillary density by more than 50%. The induced IA was accompanied by detachment of pericytes from basement membrane, increased vessel permeability and recruitment of mononuclear cells toward the pillars; the process was dramatically enhanced after injection of bone marrowderived mononuclear cells. The extravasation of mononuclear cells with eventual bone marrow origin was associated with upregulation of chemotaxis factors SDF-1 and CXCR4. In addition, SDF-1 expression was upregulated in the endothelium of liver sinusoids in Notch1 knockout mouse, together with vascular remodeling by intussusception. In this chapter, we discuss this important mechanism of angiogenesis, as well as the role of Notch signaling, SDF-1 signaling and mononuclear cells in the complex process of angiogenesis.

Decreased levels of miR-28-5p and miR-361-3p and increased levels of insulin-like growth factor 1 mRNA in mononuclear cells from patients with hereditary hemorrhagic telangiectasia

“…PBMCs, specifically the monocyte fraction, have been shown to express and secrete IGF1 in a paracrine manner to modulate and coordinate various processes, including inflammation, vascular repair, and angiogenesis (Delafontaine et al 2004; Dimova and Djonov 2017). Additionally, PBMCs have been reported to express the IGF1 receptor and are susceptible to IGF1 stimulation (Kooijman et al 1992).…”