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 thedeposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongatedglycosaminoglycan (GAG) chains. Recent studies have elucidated a...
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| Format: | Article |
| Language: | English |
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Royan Institute (ACECR), Tehran
2024-02-01
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| Series: | Cell Journal |
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| Online Access: | https://www.celljournal.org/article_709484_8fc530feb3148bbaf83bf4252ebcc377.pdf |
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| author | Hossein Ghaderi-Zefrehi Ghorban Mohammadzadeh Mojtaba Rashidi Maryam Adelipour Hossein Babaahmadi Rezaei |
| author_facet | Hossein Ghaderi-Zefrehi Ghorban Mohammadzadeh Mojtaba Rashidi Maryam Adelipour Hossein Babaahmadi Rezaei |
| author_sort | Hossein Ghaderi-Zefrehi |
| collection | DOAJ |
| description | Objective: According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to thedeposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongatedglycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growthfactor-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 knownto exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research wasto ascertain the influence of atorvastatin on TGF-β-stimulated expression of CHST11 and CHSY1 and associatedsignaling pathways using an in vitro model.Materials and Methods: In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubatedwith atorvastatin (0.1-10 μM) prior to being stimulated with TGF-β (2 ng/ml). The experiment aimed to evaluate thephosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNAexpression of CHST11 and CHSY1.Results: Our research results indicated that atorvastatin inhibited TGF-β-stimulated CHSY1 and CHST11 mRNAexpression. Further experiments showed that atorvastatin diminished TGF-β-stimulated ROS production and weakenedTGF-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 modulationof the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by whichatorvastatin exerts its pleiotropic effects against atherosclerosis. |
| first_indexed | 2024-04-25T01:25:15Z |
| format | Article |
| id | doaj.art-eb2c1b683331447c963fcba629d0ada6 |
| institution | Directory Open Access Journal |
| issn | 2228-5806 2228-5814 |
| language | English |
| last_indexed | 2024-04-25T01:25:15Z |
| publishDate | 2024-02-01 |
| publisher | Royan Institute (ACECR), Tehran |
| record_format | Article |
| series | Cell Journal |
| spelling | doaj.art-eb2c1b683331447c963fcba629d0ada62024-03-09T07:20:35ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142024-02-0126215816610.22074/cellj.2023.2010482.1397709484Atorvastatin’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 CellsHossein Ghaderi-Zefrehi0Ghorban Mohammadzadeh1Mojtaba Rashidi2Maryam Adelipour3Hossein Babaahmadi Rezaei4Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranHyperlipidemia Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranHyperlipidemia Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranDepartment of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranAtherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranObjective: According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to thedeposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongatedglycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growthfactor-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 knownto exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research wasto ascertain the influence of atorvastatin on TGF-β-stimulated expression of CHST11 and CHSY1 and associatedsignaling pathways using an in vitro model.Materials and Methods: In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubatedwith atorvastatin (0.1-10 μM) prior to being stimulated with TGF-β (2 ng/ml). The experiment aimed to evaluate thephosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNAexpression of CHST11 and CHSY1.Results: Our research results indicated that atorvastatin inhibited TGF-β-stimulated CHSY1 and CHST11 mRNAexpression. Further experiments showed that atorvastatin diminished TGF-β-stimulated ROS production and weakenedTGF-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 modulationof the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by whichatorvastatin exerts its pleiotropic effects against atherosclerosis.https://www.celljournal.org/article_709484_8fc530feb3148bbaf83bf4252ebcc377.pdfatorvastatinglycosaminoglycanssmad proteinstransforming growth factor |
| spellingShingle | Hossein Ghaderi-Zefrehi Ghorban Mohammadzadeh Mojtaba Rashidi Maryam Adelipour Hossein Babaahmadi Rezaei 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 Cell Journal atorvastatin glycosaminoglycans smad proteins transforming growth factor |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | atorvastatin glycosaminoglycans smad proteins transforming growth factor |
| url | https://www.celljournal.org/article_709484_8fc530feb3148bbaf83bf4252ebcc377.pdf |
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