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Statins decrease vascular epithelial growth factor expression via down-regulation of receptor for advanced glycation

Hiroki Tsujinaka1,2, Asako Itaya-Hironaka2, Akiyo Yamauchi2

  • 1Department of Ophthalmology, Nara Medical University, Kashihara 634-8522, Japan.

Heliyon
|October 4, 2017
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Summary
This summary is machine-generated.

Statins reduce vascular endothelial growth factor A (VEGF-A) and receptor for AGE (RAGE) expression in retinal cells damaged by hydroquinone and AGEs. This suggests statins may help prevent wet age-related macular degeneration (AMD).

Keywords:
BiochemistryBiological sciencesCell biologyOphthalmology

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Area of Science:

  • Ophthalmology and Vision Science
  • Molecular Biology
  • Pharmacology

Background:

  • Statins, inhibitors of HMG-CoA reductase, exhibit pleiotropic effects beyond cholesterol reduction.
  • Vascular Endothelial Growth Factor A (VEGF-A) plays a critical role in the pathogenesis of wet age-related macular degeneration (AMD).
  • Retinal Pigment Epithelium (RPE) cells are central to retinal health and are affected in AMD.

Purpose of the Study:

  • To investigate the effect of statins on VEGF-A expression in human RPE cells.
  • To determine the role of the Receptor for Advanced Glycation Endproducts (RAGE) in statin-mediated modulation of VEGF-A.

Main Methods:

  • Human RPE cells were treated with hydroquinone (HQ) and advanced glycation endproducts (AGEs) to model AMD in vitro.
  • Cells were subsequently treated with atorvastatin or lovastatin, and VEGF-A and RAGE expression/secretion were measured.
  • RNA interference (siRNA) targeting RAGE and promoter deletion analyses were used to elucidate mechanisms.

Main Results:

  • HQ + AGE treatment increased VEGF-A and RAGE mRNA levels and VEGF-A secretion in RPE cells.
  • Atorvastatin and lovastatin significantly attenuated HQ + AGE-induced increases in VEGF-A and RAGE expression and VEGF-A secretion.
  • RAGE knockdown and inhibition of RAGE promoter activity by statins confirmed RAGE's role in mediating VEGF-A upregulation.

Conclusions:

  • Statins effectively reduce VEGF-A expression in RPE cells, partly by decreasing RAGE expression and activity.
  • These findings suggest a potential therapeutic role for statins in preventing or managing wet AMD.
  • Statins may serve as preventive agents against wet AMD due to their inhibitory effects on key pathogenic factors like VEGF-A.