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Objective <p>Graves’ ophthalmopathy (GO) is characterized by orbital fibroblast (OF) proliferation, hyaluronic acid (HA) secretion, and inflammation. Modulating these pathological mechanisms may offer a therapeutic strategy for GO. This exploratory study aimed to investigate the effects of enalapril and losartan on gene expression related to inflammation, fibrogenesis, and apoptosis in OFs derived from a GO patient.</p> Results <p>Primary OFs were obtained from orbital tissue during decompression surgery (from a single GO patient) and treated with enalapril and losartan at concentrations of 0.5x, x, 2x, and 4x (where x = 40 ng/mL for enalapril and 400 ng/mL for losartan). Real-time PCR was used to assess expression of IL1B, IL6, THY1, HAS, TGFB, BCL2, and BAX. Both drugs significantly reduced IL1B expression at 0.5x, suggesting potential anti-inflammatory effects at low doses. However, IL6, THY1, HAS, and TGFB were either unchanged or upregulated following treatment. No cytotoxic effects were observed. The influence on apoptotic genes (BCL2 and BAX) was modest and dose-dependent. These findings suggest that enalapril and losartan may modulate inflammation in GO OFs, though their effects on fibrogenic and apoptotic pathways remain complex. Further multi-donor studies are needed to evaluate their therapeutic potential in GO.</p>

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Effect of enalapril and losartan on the expression of genes involved in inflammation, fibrogenesis, and apoptosis in orbital fibroblasts of graves’ ophthalmopathy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月27日

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  • Fatemeh Sanie-Jahromi,
  • Behzad Khademi,
  • Naser Owji

摘要

Objective

Graves’ ophthalmopathy (GO) is characterized by orbital fibroblast (OF) proliferation, hyaluronic acid (HA) secretion, and inflammation. Modulating these pathological mechanisms may offer a therapeutic strategy for GO. This exploratory study aimed to investigate the effects of enalapril and losartan on gene expression related to inflammation, fibrogenesis, and apoptosis in OFs derived from a GO patient.

Results

Primary OFs were obtained from orbital tissue during decompression surgery (from a single GO patient) and treated with enalapril and losartan at concentrations of 0.5x, x, 2x, and 4x (where x = 40 ng/mL for enalapril and 400 ng/mL for losartan). Real-time PCR was used to assess expression of IL1B, IL6, THY1, HAS, TGFB, BCL2, and BAX. Both drugs significantly reduced IL1B expression at 0.5x, suggesting potential anti-inflammatory effects at low doses. However, IL6, THY1, HAS, and TGFB were either unchanged or upregulated following treatment. No cytotoxic effects were observed. The influence on apoptotic genes (BCL2 and BAX) was modest and dose-dependent. These findings suggest that enalapril and losartan may modulate inflammation in GO OFs, though their effects on fibrogenic and apoptotic pathways remain complex. Further multi-donor studies are needed to evaluate their therapeutic potential in GO.