Inter-Alpha Inhibitor Proteins Modify the Microvasculature after Exposure to Hypoxia–Ischemia and Hypoxia in Neonatal Rats

Girolamo, Francesco; Lim, Yow‐Pin; Virgintino, Daniela; Stonestreet, Barbara S.; Chen, Xiaodi F.

doi:10.3390/ijms24076743

Cited by 4 publications

(1 citation statement)

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“…These observations support the effectiveness of the VBL in revealing pericyte conduits and P-TNTs, distinguishing them from 'string vessels', described as formed by VBL residues after endothelial cell death and vessel remodeling in stroke pathology [6]. Indeed, after exposure to experimental conditions of hypoxia and ischemia, aspects of neo-angiogenesis, characterized by P-TNT-like structures, have been detected as a tissue response and an attempt at vascular recovery [7]. Endothelium-free pericyte conduits and segments of growing sprouts were firstly revealed by Ozerdem and colleagues in mouse retina and gliomas [8,9], and have subsequently been confirmed in human developing brain and glioblastoma, where P-TNTs have also been unveiled, and appear to be involved in the pericyte-driven mode of vessel growth [1,4,[10][11][12][13].…”

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confidence: 68%

Pericyte-Tunnelling Nanotube-Driven Angiogenesis and C-KIT Immunolocalization in Human Developing Brain and Glioblastoma

Errede,

D’Amati,

Annese

et al. 2023

Preprint

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Pericyte and their tunnelling nanotubes (P-TNTs) have been described as involved in the early phases of angiogenesis in the human normal developing brain and glioblastoma, being a common feature of combined endothelium/pericyte vessel sprouts. Based on the few data available so far about this ‘alternative’ pericyte-TNT-driven mode of angiogenesis, whose precise function in vessel growth through vascular cells communication, has still to be determined, this study aims to cast light on the regulative molecules involved in this process, governed by intimate pericyte-endothelial interactions. After considering the existence of the sprout guiding pericyte and P-TNT, as shown by pioneering ultrastructural studies as well as by more recent observations with NG2/CD146 pericyte markers and basal lamina molecules, a step-by-step profile of the process has been suggested and an investigation undertaken on ‘unconventional’, pro-angiogenic ligand/receptor systems, that may have a role aside from the canonical pathways. In this context, a possible candidate worthy of investigation is the c-KIT receptor, a member of the tyrosine kinase family of proteins, which also includes the well-known VEGFR and PDGFR. According to the obtained results showing a primary localization of c-KIT on endothelial cells and pointing out a differential distribution of the receptor on normal vs glioblastoma vessels, it seems conceivable to propose the stem cell factor/c-KIT signaling as a key factor in pericyte-TNT-driven angiogenesis, advancing this alternative mode of angiogenesis and the c- KIT pathway as possible targets for devising effective antiangiogenic therapeutic strategies.

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