{"title":"阿托伐他汀在动脉粥样硬化中的治疗潜力：通过调节血管平滑肌细胞中的 ROS-ERK1/2-Smad2L 信号通路，抑制 TGF-β 诱导的蛋白多糖氨基多糖链延长。","authors":"Hossein Ghaderi-Zefrehi, Ghorban Mohammadzadeh, Mojtaba Rashidi, Maryam Adelipour, Hossein Babaahmadi Rezaei","doi":"10.22074/cellj.2023.2010482.1397","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to the deposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongated glycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growth factor-β (TGF-β) promotes the expression of genes linked to proteoglycan GAG chain elongation (<i>CHSY1</i> and <i>CHST11</i>) via reactive oxygen species (ROS) and the downstream phosphorylation of ERK1/2 and Smad2L. Atorvastatin is known to exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research was to ascertain the influence of atorvastatin on TGF-β-stimulated expression of <i>CHSY1</i> and <i>CHST11</i> and associated signaling pathways using an <i>in vitro</i> model.</p><p><strong>Materials and methods: </strong>In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubated with atorvastatin (0.1-10 μM) prior to being stimulated with TGF-β (2 ng/ml). The experiment aimed to evaluate the phosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNA expression of <i>CHST11</i> and <i>CHSY1</i>.</p><p><strong>Results: </strong>Our research results indicated that atorvastatin inhibited TGF-β-stimulated <i>CHSY1</i> and <i>CHST11</i> mRNA expression. Further experiments showed that atorvastatin diminished TGF-β-stimulated ROS production and weakened TGF-β-stimulated phosphorylation of p47phox, ERK1/2, and Smad2L; however, we observed no effect on the TGF-β- Smad2C pathway.</p><p><strong>Conclusion: </strong>These data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulation of the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by which atorvastatin exerts its pleiotropic effects against atherosclerosis.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"26 2","pages":"158-166"},"PeriodicalIF":1.7000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924836/pdf/","citationCount":"0","resultStr":"{\"title\":\"Atorvastatin's Therapeutic Potential in Atherosclerosis: Inhibiting TGF-β-Induced Proteoglycan Glycosaminoglycan Chain Elongation through ROS-ERK1/2-Smad2L Signaling Pathway Modulation in Vascular Smooth Muscle Cells.\",\"authors\":\"Hossein Ghaderi-Zefrehi, Ghorban Mohammadzadeh, Mojtaba Rashidi, Maryam Adelipour, Hossein Babaahmadi Rezaei\",\"doi\":\"10.22074/cellj.2023.2010482.1397\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to the deposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongated glycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growth factor-β (TGF-β) promotes the expression of genes linked to proteoglycan GAG chain elongation (<i>CHSY1</i> and <i>CHST11</i>) via reactive oxygen species (ROS) and the downstream phosphorylation of ERK1/2 and Smad2L. Atorvastatin is known to exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research was to ascertain the influence of atorvastatin on TGF-β-stimulated expression of <i>CHSY1</i> and <i>CHST11</i> and associated signaling pathways using an <i>in vitro</i> model.</p><p><strong>Materials and methods: </strong>In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubated with atorvastatin (0.1-10 μM) prior to being stimulated with TGF-β (2 ng/ml). The experiment aimed to evaluate the phosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNA expression of <i>CHST11</i> and <i>CHSY1</i>.</p><p><strong>Results: </strong>Our research results indicated that atorvastatin inhibited TGF-β-stimulated <i>CHSY1</i> and <i>CHST11</i> mRNA expression. Further experiments showed that atorvastatin diminished TGF-β-stimulated ROS production and weakened TGF-β-stimulated phosphorylation of p47phox, ERK1/2, and Smad2L; however, we observed no effect on the TGF-β- Smad2C pathway.</p><p><strong>Conclusion: </strong>These data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulation of the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by which atorvastatin exerts its pleiotropic effects against atherosclerosis.</p>\",\"PeriodicalId\":49224,\"journal\":{\"name\":\"Cell Journal\",\"volume\":\"26 2\",\"pages\":\"158-166\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924836/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Journal\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.22074/cellj.2023.2010482.1397\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Journal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.22074/cellj.2023.2010482.1397","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Atorvastatin's Therapeutic Potential in Atherosclerosis: Inhibiting TGF-β-Induced Proteoglycan Glycosaminoglycan Chain Elongation through ROS-ERK1/2-Smad2L Signaling Pathway Modulation in Vascular Smooth Muscle Cells.
Objective: According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to the deposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongated glycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growth factor-β (TGF-β) promotes the expression of genes linked to proteoglycan GAG chain elongation (CHSY1 and CHST11) via reactive oxygen species (ROS) and the downstream phosphorylation of ERK1/2 and Smad2L. Atorvastatin is known to exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research was to ascertain the influence of atorvastatin on TGF-β-stimulated expression of CHSY1 and CHST11 and associated signaling pathways using an in vitro model.
Materials and methods: In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubated with atorvastatin (0.1-10 μM) prior to being stimulated with TGF-β (2 ng/ml). The experiment aimed to evaluate the phosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNA expression of CHST11 and CHSY1.
Results: Our research results indicated that atorvastatin inhibited TGF-β-stimulated CHSY1 and CHST11 mRNA expression. Further experiments showed that atorvastatin diminished TGF-β-stimulated ROS production and weakened TGF-β-stimulated phosphorylation of p47phox, ERK1/2, and Smad2L; however, we observed no effect on the TGF-β- Smad2C pathway.
Conclusion: These data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulation of the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by which atorvastatin exerts its pleiotropic effects against atherosclerosis.
期刊介绍：
The “Cell Journal (Yakhteh)“, formerly published as “Yakhteh Medical Journal”, is a quarterly English publication of Royan Institute. This journal focuses on topics relevant to cellular and molecular scientific areas, besides other related fields. The Cell J has been certified by Ministry of Culture and Islamic Guidance in 1999 and was accredited as a scientific and research journal by HBI (Health and Biomedical Information) Journal Accreditation Commission in 2000 which is an open access journal.
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