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In Vitro Model of Physiological and Pathological Blood Flow with Application to Investigations of Vascular Cell Remodeling
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Intussusceptive Vascular Remodeling Precedes Pathological Neovascularization.

Zaheer Ali1, Anthony Mukwaya2, Antje Biesemeier3

  • 1From the Division of Cardiovascular Medicine, Department of Medical and Health Sciences (Z.A., L.D.J.), Linkoping University, Sweden.

Arteriosclerosis, Thrombosis, and Vascular Biology
|June 27, 2019
PubMed
Summary
This summary is machine-generated.

Pathological vascular remodeling (PVR) initiates neovascular diseases before new vessel growth. This study reveals early PVR mechanisms involving vascular intussusception and endothelial changes, offering future therapeutic targets.

Keywords:
choroidal neovascularizationhypoxiaintussusceptionmacular degenerationzebrafish

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Area of Science:

  • Ophthalmology
  • Vascular Biology
  • Cell Biology

Background:

  • Pathological neovascularization drives severe diseases like cancer and macular degeneration.
  • Early pathological vascular remodeling (PVR) events preceding neovascularization are poorly understood.

Purpose of the Study:

  • To identify novel molecular and cellular mechanisms of preneovascular PVR using the adult choriocapillaris as a model.
  • To elucidate the signaling pathways involved in hypoxia-induced PVR.

Main Methods:

  • Induction of PVR via hypoxia or VEGF overexpression in zebrafish and rats.
  • Analysis of human choroidal neovascular lesions.
  • RNA-sequencing of affected tissues.
  • Genetic manipulation in zebrafish and primary human cell culture.

Main Results:

  • Pre-neovascular PVR involves vascular intussusception, endothelial proliferation, vesiculation, and thickening.
  • Endothelial tight junction disruption, cytoskeletal remodeling, and biogenesis of vesicles/cilia are key PVR components.
  • Hypoxia-induced factor-1α (HIF-1α)-VEGF-A-VEGFR2 signaling is critical for PVR.

Conclusions:

  • PVR, characterized by specific vascular and endothelial changes, precedes neovascularization.
  • Targeting these early PVR processes may offer future strategies to prevent neovascular diseases.