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Cited by 66Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismPsoriasis: Treatment and Pathogenesis

Pioglitazone stabilizes atherosclerotic plaque by regulating the Th17/Treg balance in AMPK-dependent mechanisms

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Tian, Yuling, Chen, Tao, Wu, Yan, Yang, Lin, Wang, Lijun, Fan, Xiaojuan, Zhang, Wei, Feng, Jiahao +5 more·2017·Cardiovascular Diabetology
DOI 10.1186/s12933-017-0623-6PMC PMC5663071
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Abstract

BACKGROUND: Pioglitazone (PIO), a thiazolidinediones drug, is a well-known anti-diabetic medicine, but its anti-atherosclerotic effects remain controversial. Thus it is important to investigate the effects of PIO on atherogenesis and the relevant mechanisms. METHODS: For in vitro studies, primary cultured or AMP-activated protein kinase (AMPK) inhibited splenocytes were treated with oxidized low density lipoprotein (ox-LDL) or ox-LDL plus PIO. Percentage of T helper 17 (Th17) and regulatory T (Treg) cells were determined by flow cytometry. Expression of AMPK, interleukin-17 (IL-17) and forkhead box P3 (FoxP3) were detected by Western blots. For in vivo studies, apolipoprotein E-deficient (apoE-/-) mice fed with western diet were treated with PIO or vehicle for 8 weeks respectively. Percentage of Th17 and Treg cells in spleen were measured by immunohistochemical analysis. The atherosclerotic lesions were analyzed using oil red O staining, and collagen types I and III in atherosclerotic lesions were stained by Sirius red. Expression of IL-17 and FoxP3 were determined by quantitative polymerase chain reaction. RESULTS: cells in spleen of apoE-/- mice. Finally, PIO did not alter plaque area, but intriguingly, stabilized atherosclerotic plaque through collagen induction in apoE-/- mice. PIO treatment also improved Th17/Treg balance in atherosclerotic lesions. CONCLUSIONS: PIO exhibits anti-atherosclerotic effects for stabilization of atherosclerotic plaque through regulating the Th17/Treg balance in an AMPK-dependent manner.

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  • PPARγ agonists, such as pioglitazone, exhibit anti-inflammatory properties and are promising therapeutic candidates for enhancing adipose tissue-Tregs function and restoring immune tolerance in chronic liver diseases.

    “PPARγ agonists, such as the thiazolidinedione drug pioglitazone, exhibit anti-inflammatory properties and are considered promising therapeutic candidates for enhancing adipose tissue–Tregs function and restoring immune tolerance in chronic liver diseases (Negrotto et al. 2016; Tian et al. 2017).”

    From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Tian et al. 2017

    The Introduction describes pioglitazone as a PPARγ-agonist thiazolidinedione and discusses the class’s anti-inflammatory properties. The Discussion reports increased Treg markers in mouse spleens and cultured splenocytes after pioglitazone treatment. It does not establish enhanced adipose-tissue Treg function or propose pioglitazone to restore immune tolerance in chronic liver disease; its focus is atherosclerosis. (LLM, conf=0.88)

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Authors
Tian, Y., Chen, T., Wu, Y., Yang, L., Wang, L., Fan, X., Zhang, W., Feng, J., Yu, H., Yang, Y., Zhou, J., Yuan, Z., & Wu, Y.
Affiliations
First Affiliated Hospital of Xi'an Jiaotong University (CN)
Corresponding author
  • Yuan, Zuyi
  • Wu, Yue
ORCID
Venue
Cardiovascular Diabetology
Publisher
Springer Science and Business Media LLC
Published
2017-10-30
Volume
16
Issue
1
Pages
140-140
ISSN
1475-2840 (ISSN-L)
DOI
10.1186/s12933-017-0623-6
PMC
PMC5663071
OpenAlex
W2765767647
Cited by
66
References
42
Citations by year
2026: 8 · 2025: 7 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 11 · 2020: 7 · 2019: 10 · 2018: 3
FWCI
2.48
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cardiovascular Diabetology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81300226, 81025002)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
pioglitazone, atherosclerotic plaque stabilization, Th17/Treg balance, AMPK, thiazolidinediones, IL-17, Foxp3, oxidized LDL, collagen deposition, atherosclerosis, ApoE-deficient mice, Western diet
MeSH terms
Pioglitazone, AMP-Activated Protein Kinase Kinases, Animals, Cells, Cultured, Hypoglycemic Agents, Protein Kinases, Mice, Knockout, Thiazolidinediones, Atherosclerosis, T-Lymphocytes, Regulatory, Mice, Mice, 129 Strain, Th17 Cells

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