Combination of apolipoprotein-A-I/apolipoprotein-A-I binding protein and anti-VEGF treatment overcomes anti-VEGF resistance in choroidal neovascularization in mice. Academic Article uri icon

Overview

abstract

  • Many patients of choroidal neovascularization (CNV) are unresponsive to the current anti-VEGF treatment. The mechanisms for anti-VEGF resistance are poorly understood. We explore the unique property of the apolipoprotein A-I (apoA-I) binding protein (AIBP) that enhances cholesterol efflux from endothelial cells and macrophages to thereby limit angiogenesis and inflammation to tackle anti-VEGF resistance in CNV. We show that laser-induced CNV in mice with increased age showed increased resistance to anti-VEGF treatment, which correlates with increased lipid accumulation in macrophages. The combination of AIBP/apoA-I and anti-VEGF treatment overcomes anti-VEGF resistance and effectively suppresses CNV. Furthermore, macrophage depletion in old mice restores CNV sensitivity to anti-VEGF treatment and blunts the synergistic effect of combination therapy. These results suggest that cholesterol-laden macrophages play a critical role in inducing anti-VEGF resistance in CNV. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.

publication date

  • July 16, 2020

Research

keywords

  • Apolipoprotein A-I
  • Choroidal Neovascularization
  • Phosphoproteins
  • Racemases and Epimerases
  • Vascular Endothelial Growth Factor A

Identity

PubMed Central ID

  • PMC7367303

Scopus Document Identifier

  • 85088145818

Digital Object Identifier (DOI)

  • 10.1016/j.ajpath.2017.08.025

PubMed ID

  • 32678293

Additional Document Info

volume

  • 3

issue

  • 1