Academic Journal
GW0742 prevents neointima formation by upregulating FABP3 expression.
| Τίτλος: | GW0742 prevents neointima formation by upregulating FABP3 expression. |
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| Συγγραφείς: | Wang X; Department of Cardiology, Tongren People's Hospital, Tongren, Guizhou, China., Chen J; Division of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Huo B; Division of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Wu X; Division of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Lin W; Division of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Jiang DS; Division of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Key Laboratory of Organ Transplantation, Ministry of Education, Chinese Academy of Medical Sciences; NHC Key Laboratory of Organ Transplantation, Wuhan, Hubei, China., Zhang YS; Department of Cardiology, Tongren People's Hospital, Tongren, Guizhou, China., Feng X; Division of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: xinfengtjh@126.com., Gong FH; Department of Cardiology, Tongren People's Hospital, Tongren, Guizhou, China. Electronic address: gongfh@whu.edu.cn. |
| Πηγή: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2026 Nov 01; Vol. 226, pp. 107636. Date of Electronic Publication: 2026 Aug 12. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science B.V Country of Publication: Netherlands NLM ID: 9317982 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0720 (Electronic) Linking ISSN: 09280987 NLM ISO Abbreviation: Eur J Pharm Sci Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Science B.V Original Publication: Amsterdam ; New York : Elsevier, c1993- |
| Ιατρικοί όροι (MeSH): | Neointima*/metabolism , Neointima*/prevention & control , Neointima*/pathology , Neointima*/drug therapy , Thiazoles*/pharmacology , Thiazoles*/therapeutic use , Fatty Acid Binding Protein 3*/genetics , Fatty Acid Binding Protein 3*/metabolism, Cell Proliferation/drug effects ; Up-Regulation/drug effects ; Cell Movement/drug effects ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/metabolism ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/cytology ; Carotid Artery Injuries/drug therapy ; Carotid Artery Injuries/metabolism ; Carotid Artery Injuries/pathology ; Animals ; Male ; Humans ; Sulfhydryl Compounds ; Phenols ; Mice, Inbred C57BL ; Cells, Cultured ; Mice ; Becaplermin |
| Περίληψη: | Phenotypic switching of vascular smooth muscle cells (VSMCs), leading to neointima formation, is a main cause of in-stent restenosis after coronary stent implantation, resulting in poor patient prognosis. Inhibition of VSMC proliferation, migration, and synthetic phenotype transition holds promise for preventing and treating neointimal hyperplasia and restenosis. GW0742, a peroxisome proliferator-activated receptor (PPAR)-β/δ agonist, has been reported to suppress atherosclerosis and myocardial ischemia-reperfusion injury. However, its role in neointima formation has not been previously studied. In this study, we found that GW0742 significantly inhibited carotid artery injury-induced neointimal hyperplasia in mice. In vitro experiments including cell counting, EdU staining, and proliferation marker detection revealed that GW0742 markedly suppressed Platelet-derived growth factor-BB (PDGF-BB)-induced proliferation of human aortic smooth muscle cells (HASMCs). Flow cytometry analysis showed that GW0742 treatment arrested cells in the G2/M phase. Transwell assays demonstrated that GW0742 inhibited HASMCs migration. Moreover, GW0742 reduced the expression of migration-associated proteins matrix metalloproteinases 2 (MMP2) and matrix metalloproteinases 9 (MMP9), while increasing contractile markers alpha-smooth muscle actin (α-SMA) and calponin 1 (CNN1), suggesting that GW0742 suppresses HASMC proliferation, migration, and phenotypic switching, thereby preserving the contractile phenotype. RNA sequencing revealed that GW0742 regulates fatty acid metabolism by upregulating fatty acid binding protein 3 (FABP3) expression to counteract PDGF-BB-induced VSMC phenotypic switching. Knockdown of FABP3 significantly abrogated the inhibitory effects of GW0742 on VSMC proliferation, migration, and synthetic phenotype transition. Taken together, our findings demonstrate that GW0742 upregulates FABP3 expression, leading to the inhibition of VSMC proliferation, migration, and phenotypic switching, and ultimately suppressing neointima formation. These results underscore the therapeutic potential of GW0742 for the prevention and treatment of vascular restenosis. (Copyright © 2026 The Author(s). Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Competing interests The authors declare that they have no competing interests. |
| Contributed Indexing: | Keywords: FABP3; GW0742; Neointima formation; PPAR-β/δ |
| Substance Nomenclature: | 4PZK9FJC4Z ((4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid) 0 (Thiazoles) 0 (Sulfhydryl Compounds) 0 (Phenols) 0 (Fatty Acid Binding Protein 3) 1B56C968OA (Becaplermin) |
| Entry Date(s): | Date Created: 20260812 Date Completed: 20260909 Latest Revision: 20260909 |
| Update Code: | 20260910 |
| DOI: | 10.1016/j.ejps.2026.107636 |
| PMID: | 42586383 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1879-0720 |
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| DOI: | 10.1016/j.ejps.2026.107636 |