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


ABSTRACT: AIMS:Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, possess pleiotropic effects that have been extended to modulation of various cellular behaviors. This study aimed to examine whether statins modulate vascular endothelial growth factor A (VEGF-A) expression in human retinal pigment epithelium (RPE) cells. MAIN METHODS:Human RPE cells (h1RPE7), damaged by hydroquinone (HQ) + advanced glycation endproducts (AGE) in an in vitro AMD model, were treated with atorvastatin or lovastatin for 24 h. The expression of VEGF-A and receptor for AGE (RAGE) was evaluated by real-time RT-PCR. VEGF-A secretion was measured by ELISA. To investigate the impact of RAGE on VEGF-A expression, small interfering RNA (siRNA) for RAGE (siRAGE) was introduced into h1RPE7 cells and VEGF-A expression was measured by real-time RT-PCR. Deletions of VEGF-A and RAGE promoters were performed and transcriptional activities were measured after the addition of statins to HQ + AGE-damaged RPE cells. KEY FINDINGS:The mRNA levels of VEGF-A and RAGE and the levels of VEGF-A in the culture medium were increased by HQ + AGE. Both atorvastatin and lovastatin attenuated HQ + AGE-induced VEGF-A and RAGE expression. These statins also decreased VEGF-A levels in the culture medium. RNA interference of RAGE attenuated the up-regulation of VEGF-A in the HQ + AGE treated cells. The deletion analysis demonstrated that these statins attenuated RAGE promoter activation in HQ + AGE-damaged RPE cells. SIGNIFICANCE:Statins attenuated HQ + AGE-induced VEGF expression by decreasing RAGE expression. As VEGF is an important factor in developing wet AMD, statins could decrease the risk of wet-type AMD and be used as preventive medicines.

SUBMITTER: Tsujinaka H 

PROVIDER: S-EPMC5612812 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Tsujinaka Hiroki H   Itaya-Hironaka Asako A   Yamauchi Akiyo A   Sakuramoto-Tsuchida Sumiyo S   Shobatake Ryogo R   Makino Mai M   Masuda Naonori N   Hirai Hiromasa H   Takasawa Shin S   Ogata Nahoko N  

Heliyon 20170922 9


<h4>Aims</h4>Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, possess pleiotropic effects that have been extended to modulation of various cellular behaviors. This study aimed to examine whether statins modulate vascular endothelial growth factor A (<i>VEGF-A</i>) expression in human retinal pigment epithelium (RPE) cells.<h4>Main methods</h4>Human RPE cells (h1RPE7), damaged by hydroquinone (HQ) + advanced glycation endproducts (AGE) in an <i>in vitro</i> AMD model, were  ...[more]

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