ArticleBiochemical pharmacology2016
Pioglitazone, a PPARγ agonist, attenuates PDGF-induced vascular smooth muscle cell proliferation through AMPK-dependent and AMPK-independent inhibition of mTOR/p70S6K and ERK signaling.
Article in Biochemical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Hepatic control of immunometabolism: implications for the pathogenesis, diagnosis and treatment of rheumatic diseases.Nature reviews. Rheumatology · 2026Review
- An overview of the role of platelets in vascular disease associated with diabetes mellitus.Hormones (Athens, Greece) · 2026Review
- Exercise-Induced Muscle-Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Differential expression of PPARγ by pioglitazone and telmisartan causes effect of disparity on mTORC2-mediated cell proliferation and migration.Scientific reports · 2025Article
- PPAR-γ in Melanoma and Immune Cells: Insights into Disease Pathogenesis and Therapeutic Implications.Cells · 2025Review
- PPARs in atherosclerosis: The spatial and temporal features from mechanism to druggable targets.Journal of advanced research · 2025Review
- Far-infrared irradiation inhibits proliferation of human upper airway epithelial cells via protein phosphatase 2A-promoted dephosphorylation of p70 S6 kinase.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2024Article
- Far-infrared irradiation inhibits proliferation of human upper airway epithelial cells via protein phosphatase 2A-promoted dephosphorylation of p70 S6 kinase.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2024Article
- Gut microbiota-derived Metabolite, Shikimic Acid, inhibits vascular smooth muscle cell proliferation and migration.Biochemical pharmacology · 2024Article
- Far-Infrared Irradiation Decreases Proliferation in Basal and PDGF-Stimulated VSMCs Through AMPK-Mediated Inhibition of mTOR/p70S6K Signaling Axis.Journal of Korean medical science · 2023Article
- Adipokines in atherosclerosis: unraveling complex roles.Frontiers in cardiovascular medicine · 2023Review
- Six Decades of History of Hypertension Research at the University of Toledo: Highlighting Pioneering Contributions in Biochemistry, Genetics, and Host-Microbiota Interactions.Current hypertension reports · 2022Review
- LKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP axis.Bosnian journal of basic medical sciences · 2022Article
- The Role of Peroxisome Proliferator-Activated Receptor Gamma and Atherosclerosis: Post-translational Modification and Selective Modulators.Frontiers in physiology · 2022Review
- The critical issue linking lipids and inflammation: Clinical utility of stopping oxidative stress.Frontiers in cardiovascular medicine · 2022Review
- Article
- Adropin inhibits the phenotypic modulation and proliferation of vascular smooth muscle cells during neointimal hyperplasia by activating the AMPK/ACC signaling pathway.Experimental and therapeutic medicine · 2021Article
- Phosphorylated proteomics analysis of human coronary artery endothelial cells stimulated by Kawasaki disease patients serum.BMC cardiovascular disorders · 2019Article
- Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory responses through activation of AMP-activated protein kinase (AMPK) signaling.Arthritis research & therapy · 2018Article
- A Sterol from Soft Coral Induces Apoptosis and Autophagy in MCF-7 Breast Cancer Cells.Marine drugs · 2018Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Pioglitazone (PIO), a PPARγ agonist that improves glycemic control in type 2 diabetes through its insulin-sensitizing action, has been shown to exhibit beneficial effects in the vessel wall. For instance, it inhibits vascular smooth muscle cell (VSMC) proliferation, a major event in atherosclerosis and restenosis after angioplasty. Although PPARγ-dependent and PPARγ-independent mechanisms have been attributed to its vasoprotective effects, the signaling events associated with PIO action in VSMCs are not fully understood. To date, the likely intermediary role of AMP-activated protein kinase (AMPK) toward PIO inhibition of VSMC proliferation has not been examined. Using human aortic VSMCs, the present study demonstrates that PIO activates AMPK in a sustained manner thereby contributing in part to inhibition of key proliferative signaling events. In particular, PIO at 30μM concentration activates AMPK to induce raptor phosphorylation, which diminishes PDGF-induced mTOR activity as evidenced by decreased phosphorylation of p70S6K, 4E-BP1, and S6 and increased accumulation of p27(kip1), a cell cycle inhibitor. In addition, PIO inhibits the basal phosphorylation of ERK in VSMCs. Downregulation of endogenous AMPK by target-specific siRNA reveals an AMPK-independent effect for PIO inhibition of ERK, which contributes in part to diminutions in cyclin D1 expression and Rb phosphorylation and the suppression of VSMC proliferation. Furthermore, AMPK-dependent inhibition of mTOR/p70S6K and AMPK-independent inhibition of ERK signaling occur regardless of PPARγ expression/activation in VSMCs as evidenced by gene silencing and pharmacological inhibition of PPARγ. Strategies that utilize nanoparticle-mediated PIO delivery at the lesion site may limit restenosis after angioplasty without inducing PPARγ-mediated systemic adverse effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.