Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
November-2025 Volume 56 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2025 Volume 56 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Mechanosensor Piezo1‑mediated smooth muscular cell pyroptosis contributes to vascular calcification

  • Authors:
    • Jun Tao
    • Daiting You
    • Zejiang Feng
    • Huangjing Li
    • Yao Zhang
    • Yuting Cui
    • Kaiyuan Lin
    • Bin Luo
    • Shengli Yin
    • Hongmei Tan
  • View Affiliations / Copyright

    Affiliations: Department of Pathophysiology, School of Medicine, Shenzhen Campus of Sun Yat‑sen University, Shenzhen, Guangdong 518107, P.R. China, Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Cardiac Surgery, Hui Ya Hospital of The First Affiliated Hospital, Sun Yat‑sen University, Huizhou, Guangdong 516081, P.R. China
    Copyright: © Tao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 196
    |
    Published online on: September 11, 2025
       https://doi.org/10.3892/ijmm.2025.5637
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Vascular calcification is a pathological consequence of chronic inflammation and phenotypic switching in smooth muscle cells (SMCs). However, the mechanisms underlying vascular calcification remain unclear. The present study explores the role of the mechanosensor channel, Piezo1, in regulating vascular SMC (VSMC) death and vascular calcification. The findings of the present study demonstrated that Piezo1 expression is upregulated in the atherosclerotic plaques of both mice and patients. In vitro experiments revealed that calcifying medium (CM) induced an increase in Piezo1 and runt‑related transcription factor 2 (RUNX2) expression, triggered pyroptosis in cultured VSMCs and promoted calcium deposition in arterial rings. These effects were mitigated by a Piezo1 inhibitor and exacerbated by a Piezo1 agonist. Furthermore, gene deletion of NLR family pyrin domain containing 3 (NLRP3), caspase1 or gasdermin D also reduced CM‑induced pyroptosis and calcium deposition in VSMCs. Immunoprecipitation assays showed that calcium/calmodulin dependent protein kinase II (CaMKII), a downstream effector of Piezo1, interacted with RUNX2, and CaMKII inhibition attenuated both pyroptosis and calcification in VSMCs exposed to CM. The role of Piezo1 in mediating VSMC pyroptosis and vascular calcification was confirmed in a mouse model, where VSMC‑specific deletion of Piezo1 inhibited arterial calcification in chronic kidney disease. In conclusion, Piezo1 is a key regulator of vascular calcification via Ca2+‑CaMKII‑mediated activation of the NLRP3 inflammasome and subsequent VSMC pyroptosis.
View Figures

Figure 1

Piezo1 is upregulated in
atherosclerosis plaques in both patients and mice. (A)
Representative immunofluorescence stained images of aortic tissues
isolated from Apolipoprotein E−/− mice (scale bars, 200
μm). Piezo1 is shown in green and DAPI is shown in blue; n=6
rats per group. (B) Relative mRNA expression of Piezo1 in human
carotid samples (data from GEO dataset, GSE43292; paired t-test;
n=32); ****P<0.0001 vs. MIT. Statistical significance
of mRNA expression was assessed by paired Student's t-test (C)
VSMCs were treated with oxLDL for 24 h, and Piezo1 protein
expression was determined by western blot; *P<0.05,
**P<0.01 vs. control. Statistical significance was
assessed by one-way ANOVA followed by Tukey's. (D) Representative
immunofluorescence stained images of Piezo1 (green) in VSMCs (scar
bar, 20 μm). Cell nuclei were counterstained with DAPI
(blue). All values are presented as mean ± SD. AP, atheroma plaque;
MIT, macroscopically intact tissue; oxLDL, oxidized low-density
lipoprotein; HFD, high-fat diet; VSMCs, vascular smooth muscle
cells.

Figure 2

CM-induced osteogenic differentiation
is associated with Piezo1 expression, NLRP3 inflammasome activation
and pyroptosis in the aortic ring and VSMCs. (A) Representative
H&E staining and immunofluorescence images alongside (B and C)
quantification of α-SMA and Piezo1 expression in the aortic
sections of mice (HE scale bars, 100 μm; immunofluorescence
scale bars, 200 μm); ****P<0.0001 vs. GM.
Statistical significance of mRNA expression was assessed by
unpaired Student's t-test (D-F) Representative immunoblot images
and semi-quantification of Piezo1, ALP, BMP2, RUNX2, NLRP3,
pro-caspase1, cleaved-caspase1, GSDMD, GSDMD-NT, pro-IL-1β,
cleaved-IL-1β, cleaved caspase1/total-caspase1, GSDMD-NT/total
GSDMD and cleaved IL-1β/total IL-1β in mouse VSMC extracts. β-actin
was used as a loading control; *P<0.05,
**P<0.01, ***P<0.001,
****P<0.0001 vs. GM. Statistical significance was
assessed by one-way ANOVA followed by Tukey's. Correlation analysis
between Piezo1 protein expression and the (G) RUNX2 and (H) IL-1β
level. Pearson's correlation analysis coefficient was employed for
correlation analysis. (I) MMP changes were monitored by
fluorescence using JC-1 staining. (J) Representative
immunofluorescence images of inflammasome marker NLRP3 and ASC
expression in the VSMCs of mice. Scale bars, 10 μm; n=3
independent experiments; ***P<0.001 vs. GM. All
values are presented as mean ± SD. CM, calcifying medium; GM,
growth medium; NLRP3, NOD-like receptor thermal protein
domain-containing protein 3; VSMCs, vascular smooth muscle cells;
α-SMA, α-smooth muscle actin; ALP, alkaline phosphatase; BMP2, bone
morphogenetic protein 2; RUNX2, runt-related transcription factor
2; GSDMD, gasdermin D; GSDMD-NT, gasdermin D N-terminal; IL-1β,
interleukin-1β; MMP, mitochondrial membrane potential; ASC,
apoptosis-associated speck-like protein containing a caspase
recruitment domain.

Figure 3

Specific knockout of Piezo1 in VSMCs
alleviates arterial calcification in mice. (A) Schematic
representation of the arterial calcification in vivo
protocol. (B) Representative echocardiographic recordings revealed
that HAD induced cardiac dysfunction in VSMC-specific Piezo1
knockout mice (generated via AAV-SMA22α-cre). Cardiac dysfunction
was evaluated using echocardiographic parameters including EF, FS
and CO; ***P<0.001, ****P<0.0001. (C)
Representative 2D B-mode images from the in vivo ultrasound
scanning of the aortic arch, thoracic aorta and abdominal aorta.
White arrows indicate vascular calcifications. (D and E)
Representative images of Alizarin red staining revealed that a
HAD-induced calcium deposition in the aorta (reddish signal) of
VSMC-specific Piezo1 knockout mice. The whole-aorta analysis
further confirmed calcification extent; ****P<0.0001.
(F) Recorded aortic thickness; *P<0.05,
**P<0.01. Statistical significance was assessed by
one-way ANOVA followed by Tukey's. All values are presented as mean
± SD. AAV, adeno-associated virus; HAD, high-adenine diet; w,
weeks; EF, ejection fraction; FS, fraction shortening; CO, cardiac
output; VSMC, vascular smooth muscle cells.

Figure 4

Piezo1 inhibition blocks CM-induced
NLRP3 inflammasome activation and pyroptosis and alleviates
calcification. (A and B) Representative HE staining, Von Kossa
staining and quantification of the Von Kossa positive area in the
aortic sections of mice (scale bars, 200 μm);
*P<0.05. (C and D) TUNEL staining analysis was used
to evaluate cell death (scale bars, 200 μm);
*P<0.05. (E and F) Representative images of Alizarin
red S staining showing calcium nodule formation (reddish signal) in
VSMCs cultured with GM/CM under Piezo1 inhibitor treatment (scale
bars, 200 μm); ****P<0.0001; n=3 independent
experiments. (G-J) Representative immunoblot images of Piezo1, ALP,
BMP2, RUNX2, NLRP3, pro-caspase1, cleaved-caspase1, GSDMD,
GSDMD-NT, pro-IL-1β, cleaved-IL-1β, cleaved
caspase1/total-caspase1, GSDMD-NT/total GSDMD and cleaved
IL-1β/total IL-1β in mouse VSMC extracts. β-actin was used as a
loading control. **P<0.01, ***P<0.001,
****P<0.0001. Statistical significance was assessed
by one-way ANOVA followed by Tukey's. All values are presented as
mean ± SD. CM, calcifying medium; GM, growth medium; VK, von kossa;
TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick-end
labeling; VSMCs, vascular smooth muscle cells; ALP, alkaline
phosphatase; BMP2, bone morphogenetic protein 2; RUNX2,
runt-related transcription factor 2; NLRP3, NOD-like receptor
thermal protein domain-containing protein 3; GSDMD, gasdermin D;
GSDMD-NT, gasdermin D N-terminal; IL-1β, interleukin-1β; siRNA,
small interfering RNA.

Figure 5

Piezo1 activator promotes CM-induced
NLRP3 inflammasome activation and pyroptosis and enhances
calcification. (A and B) Representative HE staining, Von Kossa
staining and quantification of the Von Kossa positive area in the
aortic sections of mice (scale bars, 200 μm);
*P<0.05. (C and D) TUNEL staining analysis was used
to evaluate cell death (scale bars, 200 μm);
*P<0.05, ****P<0.0001. (E and F)
Calcium deposition was visualized by Alizarin red S staining at the
light microscopic level (scale bars, 200 μm);
****P<0.0001; n=3 independent experiments. (G-I)
Representative immunoblot images of Piezo1, ALP, BMP2, RUNX2,
NLRP3, pro-caspase1, cleaved-caspase1, GSDMD, GSDMD-NT, pro-IL-1β,
cleaved-IL-1β, cleaved caspase1/total-caspase1, GSDMD-NT/total
GSDMD and cleaved IL-1β/total IL-1β in mouse VSMC extracts. β-actin
was used as a loading control. *P<0.05,
**P<0.01, ***P<0.001,
****P<0.0001. Statistical significance was assessed
by one-way ANOVA followed by Tukey's. All values are presented as
mean ± SD. CM, calcifying medium; GM, growth medium; VK, von kossa;
TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick-end
labeling; ALP, alkaline phosphatase; BMP2, bone morphogenetic
protein 2; RUNX2, runt-related transcription factor 2; NLRP3,
NOD-like receptor thermal protein domain-containing protein 3;
GSDMD, gasdermin D; GSDMD-NT, gasdermin D N-terminal; IL-1β,
interleukin-1β; VSMC, vascular smooth muscle cells.

Figure 6

NLRP3, caspase1 or GSDMD deletion
inhibits CM-induced calcification with/without Piezo1 agonist. (A
and B) Representative HE staining, Von Kossa staining and
quantification of the Von Kossa positive area in the aortic
sections of NLRP3−/−, caspase1−/− and
GSDMD−/− mice (scale bars, 200 μm);
****P<0.0001 vs. CM. (C and D) TUNEL staining
analysis was used to evaluate cell death (scale bars, 200
μm); ****P<0.0001 vs. CM. (E and F) Calcium
deposition in VSMCs was visualized by Alizarin red S staining at
the light microscopic level (scale bars, 200 μm);
****P<0.0001. Statistical significance was assessed
by one-way ANOVA followed by Tukey's. All values are presented as
mean ± SD. CM, calcifying medium; GM, growth medium; VK, von kossa;
TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick-end
labeling; NLRP3, NOD-like receptor thermal protein
domain-containing protein 3; GSDMD, gasdermin D; VSMC, vascular
smooth muscle cells.

Figure 7

CaMKII promotes CM-induced calcium
deposits via binding RUNX2 in VSMCs. (A and B)
Co-immunoprecipitation of CaMKII with RUNX2 in VSMCs. (C)
Representative immunofluorescence images of CaMKII and RUNX2 in
VSMCs (scale bars, 20 μm). (D) Calcium deposition of VSMCs
was visualized in 24-well plate by Alizarin red S staining at the
light microscopic level; ***P<0.001,
****P<0.0001. (E-G) Representative immunoblot images
of Piezo1, ALP, BMP2, RUNX2, NLRP3, pro-caspase1, cleaved-caspase1,
GSDMD, GSDMD-NT, pro-IL-1β, cleaved-IL-1β, cleaved
caspase1/total-caspase1, GSDMD-NT/total GSDMD and cleaved
IL-1β/total IL-1β in mouse VSMC extracts. β-actin was used as a
loading control. *P<0.05, **P<0.01,
***P<0.001, ****P<0.0001. Statistical
significance was assessed by one-way ANOVA followed by Tukey's. All
values are presented as mean ± SD. CM, calcifying medium; GM,
growth medium; CaMKII, calcium/calmodulin dependent protein kinase
II; VSMCs, vascular smooth muscle cells; IP, immunoprecipitation;
ALP, alkaline phosphatase; BMP2, bone morphogenetic protein 2;
RUNX2, runt-related transcription factor 2; NLRP3, NOD-like
receptor thermal protein domain-containing protein 3; GSDMD,
gasdermin D; GSDMD-NT, gasdermin D N-terminal; IL-1β,
interleukin-1β.

Figure 8

Piezo1 inhibition alleviates HASMC
differentiation into osteoblasts. (A) Representative immunoblot
images of Piezo1 in HASMC extracts. β-actin was used as a loading
control; ***P<0.001. Statistical significance of mRNA
expression was assessed by unpaired Student's t-test (B) Calcium
deposition of HASMCs was visualized in 24-well plate by Alizarin
red S staining at the light microscopic level;
***P<0.001, ****P<0.0001. (C-E)
Representative immunoblot images of Piezo1, ALP, BMP2, RUNX2,
NLRP3, pro-caspase1, cleaved-caspase1, GSDMD, GSDMD-NT, pro-IL-1β,
cleaved-IL-1β, cleaved caspase1/total-caspase1, GSDMD-NT/total
GSDMD and cleaved IL-1β/total IL-1β in HASMCs extracts. β-actin was
used as a loading control; *P<0.05,
**P<0.01, ****P<0.0001. Statistical
significance was assessed by one-way ANOVA followed by Tukey's. All
values are presented as mean ± SD. HASMC, human aortic smooth
muscle cells; CM, calcifying medium; GM, growth medium; ALP,
alkaline phosphatase; BMP2, bone morphogenetic protein 2; RUNX2,
runt-related transcription factor 2; NLRP3, NOD-like receptor
thermal protein domain-containing protein 3; GSDMD, gasdermin D;
GSDMD-NT, gasdermin D N-terminal; IL-1β, interleukin-1β.

Figure 9

Potential mechanisms by which Piezo1
activation contributes to calcification in VSMCs. Piezo1 promotes
vascular calcification by activating Ca2+-CaMKII
signaling, which triggers NLRP3 inflammasome formation and induces
pyroptosis in VSMCs. VSMCs, vascular smooth muscle cells; CaMKII,
calcium/calmodulin dependent protein kinase II; NLRP3, NOD-like
receptor thermal protein domain-containing protein 3; ASC,
apoptosis-associated speck-like protein containing a caspase
recruitment domain; RUNX2, runt-related transcription factor 2;
GSDMD, gasdermin D; GSDMD-NT, gasdermin D N-terminal; IL-1β,
interleukin-1β.
View References

1 

Lanzer P, Boehm M, Sorribas V, Thiriet M, Janzen J, Zeller T, St Hilaire C and Shanahan C: Medial vascular calcification revisited: Review and perspectives. Eur Heart J. 35:1515–1525. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Ouyang L, Su X, Li W, Tang L, Zhang M, Zhu Y, Xie C, Zhang P, Chen J and Huang H: ALKBH1-demethylated DNA N6-methyladenine modification triggers vascular calcification via osteogenic reprogramming in chronic kidney disease. J Clin Invest. 131:e1469852021. View Article : Google Scholar : PubMed/NCBI

3 

Pazár B, Ea HK, Narayan S, Kolly L, Bagnoud N, Chobaz V, Roger T, Lioté F, So A and Busso N: Basic calcium phosphate crystals induce monocyte/macrophage IL-1β secretion through the NLRP3 inflammasome in vitro. J Immunol. 186:2495–2502. 2011. View Article : Google Scholar

4 

Agharazii M, St-Louis R, Gautier-Bastien A, Ung RV, Mokas S, Larivière R and Richard DE: Inflammatory cytokines and reactive oxygen species as mediators of chronic kidney disease-related vascular calcification. Am J Hypertens. 28:746–755. 2015. View Article : Google Scholar

5 

Cookson BT and Brennan MA: Pro-inflammatory programmed cell death. Trends Microbiol. 9:113–114. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Toldo S and Abbate A: The NLRP3 inflammasome in acute myocardial infarction. Nat Rev Cardiol. 15:203–214. 2018. View Article : Google Scholar

7 

Strowig T, Henao-Mejia J, Elinav E and Flavell R: Inflammasomes in health and disease. Nature. 481:278–286. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F and Shao F: Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 526:660–665. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Zeng C, Wang R and Tan H: Role of pyroptosis in cardiovascular diseases and its therapeutic implications. Int J Biol Sci. 15:1345–1357. 2019. View Article : Google Scholar : PubMed/NCBI

10 

Burger F, Baptista D, Roth A, da Silva RF, Montecucco F, Mach F, Brandt KJ and Miteva K: NLRP3 inflammasome activation controls vascular smooth muscle cells phenotypic switch in atherosclerosis. Int J Mol Sci. 23:3402021. View Article : Google Scholar

11 

Takahashi M: NLRP3 inflammasome as a common denominator of atherosclerosis and abdominal aortic aneurysm. Circ J. 85:2129–2136. 2021. View Article : Google Scholar : PubMed/NCBI

12 

Ranade SS, Qiu Z, Woo SH, Hur SS, Murthy SE, Cahalan SM, Xu J, Mathur J, Bandell M, Coste B, et al: Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc Natl Acad Sci USA. 111:10347–10352. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Li J, Hou B, Tumova S, Muraki K, Bruns A, Ludlow MJ, Sedo A, Hyman AJ, McKeown L, Young RS, et al: Piezo1 integration of vascular architecture with physiological force. Nature. 515:279–282. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Retailleau K, Duprat F, Arhatte M, Ranade SS, Peyronnet R, Martins JR, Jodar M, Moro C, Offermanns S, Feng Y, et al: Piezo1 in smooth muscle cells is involved in hypertension-dependent arterial remodeling. Cell Rep. 13:1161–1171. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Rode B, Shi J, Endesh N, Drinkhill MJ, Webster PJ, Lotteau SJ, Bailey MA, Yuldasheva NY, Ludlow MJ, Cubbon RM, et al: Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance. Nat Commun. 8:350. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Wang S, Chennupati R, Kaur H, Iring A, Wettschureck N and Offermanns S: Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release. J Clin Invest. 126:4527–4536. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Geng J, Shi Y, Zhang J, Yang B, Wang P, Yuan W, Zhao H, Li J, Qin F, Hong L, et al: TLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection. Nat Commun. 12:35192021. View Article : Google Scholar : PubMed/NCBI

18 

Barkai U, Prigent-Tessier A, Tessier C, Gibori GB and Gibori G: Involvement of SOCS-1, the suppressor of cytokine signaling, in the prevention of prolactin-responsive gene expression in decidual cells. Mol Endocrinol. 14:554–563. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Hughes K, Edin S, Antonsson A and Grundstrom T: Calmodulin-dependent kinase II mediates T cell receptor/CD3- and phorbol ester-induced activation of IkappaB kinase. J Biol Chem. 276:36008–36013. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Qian W, Hadi T, Silvestro M, Ma X, Rivera CF, Bajpai A, Li R, Zhang Z, Qu H, Tellaoui RS, et al: Microskeletal stiffness promotes aortic aneurysm by sustaining pathological vascular smooth muscle cell mechanosensation via Piezo1. Nat Commun. 13:5122022. View Article : Google Scholar : PubMed/NCBI

21 

Liu S, Tao J, Duan F, Li H and Tan H: HHcy induces pyroptosis and atherosclerosis via the lipid raft-mediated NOX-ROS-NLRP3 inflammasome pathway in apoE−/− mice. Cells. 11:24382022. View Article : Google Scholar

22 

Zeng C, Duan F, Hu J, Luo B, Huang B, Lou X, Sun X, Li H, Zhang X, Yin S and Tan H: NLRP3 inflammasome-mediated pyroptosis contributes to the pathogenesis of non-ischemic dilated cardiomyopathy. Redox Biol. 34:1015232020. View Article : Google Scholar : PubMed/NCBI

23 

American Veterinary Medical Association (AVMA): AVMA guidelines for the euthanasia of animals: 2020 Edition. American Veterinary Medical Association; Schaumburg, IL: 2020

24 

Guo Y, Tang Z, Yan B, Yin H, Tai S, Peng J, Cui Y, Gui Y, Belke D, Zhou S and Zheng XL: PCSK9 (proprotein convertase subtilisin/kexin type 9) triggers vascular smooth muscle cell senescence and apoptosis: implication of its direct role in degenerative vascular disease. Arterioscler Thromb Vasc Biol. 42:67–86. 2022. View Article : Google Scholar

25 

Ayari H and Bricca G: Identification of two genes potentially associated in iron-heme homeostasis in human carotid plaque using microarray analysis. J Biosci. 38:311–315. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Chen YW, Pat B, Gladden JD, Zheng J, Powell P, Wei CC, Cui X, Husain A and Dell'italia LJ: Dynamic molecular and histopathological changes in the extracellular matrix and inflammation in the transition to heart failure in isolated volume overload. Am J Physiol Heart Circ Physiol. 300:H2251–H2260. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Durham AL, Speer MY, Scatena M, Giachelli CM and Shanahan CM: Role of smooth muscle cells in vascular calcification: Implications in atherosclerosis and arterial stiffness. Cardiovasc Res. 114:590–600. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Zeng P, Yang J, Liu L, Yang X, Yao Z, Ma C, Zhu H, Su J, Zhao Q, Feng K, et al: ERK1/2 inhibition reduces vascular calcification by activating miR-126-3p-DKK1/LRP6 pathway. Theranostics. 11:1129–1146. 2021. View Article : Google Scholar : PubMed/NCBI

29 

Zhang X, Li Y, Yang P, Liu X, Lu L, Chen Y, Zhong X, Li Z, Liu H, Ou C, et al: Trimethylamine-N-Oxide promotes vascular calcification through activation of NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome and NF-κB (nuclear factor κB) signals. Arterioscler Thromb Vasc Biol. 40:751–765. 2020. View Article : Google Scholar : PubMed/NCBI

30 

Pang Q, Wang P, Pan Y, Dong X, Zhou T, Song X and Zhang A: Irisin protects against vascular calcification by activating autophagy and inhibiting NLRP3-mediated vascular smooth muscle cell pyroptosis in chronic kidney disease. Cell Death Dis. 13:2832022. View Article : Google Scholar : PubMed/NCBI

31 

Eapen A, Kulkarni R, Ravindran S, Ramachandran A, Sundivakkam P, Tiruppathi C and George A: Dentin phosphophoryn activates Smad protein signaling through Ca2+-calmodulin-dependent protein kinase II in undifferentiated mesenchymal cells. J Biol Chem. 288:8585–8595. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Guan Y, Chen Q, Yang X, Haines P, Pei M, Terek R, Wei X, Zhao T and Wei L: Subcellular relocation of histone deacetylase 4 regulates growth plate chondrocyte differentiation through Ca2+/calmodulin-dependent kinase IV. Am J Physiol Cell Physiol. 303:C33–C40. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Jiang M, Zhang YX, Bu WJ, Li P, Chen JH, Cao M, Dong YC, Sun ZJ and Dong DL: Piezo1 channel activation stimulates ATP production through enhancing mitochondrial respiration and glycolysis in vascular endothelial cells. Br J Pharmacol. 180:1862–1877. 2023. View Article : Google Scholar : PubMed/NCBI

34 

Solis AG, Bielecki P, Steach HR, Sharma L, Harman CCD, Yun S, de Zoete MR, Warnock JN, To SDF, York AG, et al: Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature. 573:69–74. 2019. View Article : Google Scholar : PubMed/NCBI

35 

Maldonado N, Kelly-Arnold A, Laudier D, Weinbaum S and Cardoso L: Imaging and analysis of microcalcifications and lipid/necrotic core calcification in fibrous cap atheroma. Int J Cardiovasc Imaging. 31:1079–1087. 2015. View Article : Google Scholar : PubMed/NCBI

36 

Yang Y, Wang D, Zhang C, Yang W, Li C, Gao Z, Pei K and Li Y: Piezo1 mediates endothelial atherogenic inflammatory responses via regulation of YAP/TAZ activation. Hum Cell. 35:51–62. 2022. View Article : Google Scholar

37 

Szabó L, Balogh N, Tóth A, Angyal Á, Gönczi M, Csiki DM, Tóth C, Balatoni I, Jeney V, Csernoch L and Dienes B: The mechanosensitive Piezo1 channels contribute to the arterial medial calcification. Front Physiol. 13:10372302022. View Article : Google Scholar : PubMed/NCBI

38 

Wang YM, Chu TJ, Wan RT, Niu WP, Bian YF and Li J: Quercetin ameliorates atherosclerosis by inhibiting inflammation of vascular endothelial cells via Piezo1 channels. Phytomedicine. 132:1558652024. View Article : Google Scholar : PubMed/NCBI

39 

Kelly-Arnold A, Maldonado N, Laudier D, Aikawa E, Cardoso L and Weinbaum S: Revised microcalcification hypothesis for fibrous cap rupture in human coronary arteries. Proc Natl Acad Sci USA. 110:10741–10746. 2013. View Article : Google Scholar : PubMed/NCBI

40 

Zhang K, Zhang Y, Feng W, Chen R, Chen J, Touyz RM, Wang J and Huang H: Interleukin-18 enhances vascular calcification and osteogenic differentiation of vascular smooth muscle cells through TRPM7 activation. Arterioscler Thromb Vasc Biol. 37:1933–1943. 2017. View Article : Google Scholar : PubMed/NCBI

41 

Ning FL, Tao J, Li DD, Tian LL, Wang ML, Reilly S, Liu C, Cai H, Xin H and Zhang XM: Activating BK channels ameliorates vascular smooth muscle calcification through Akt signaling. Acta Pharmacol Sin. 43:624–633. 2022. View Article : Google Scholar :

42 

Jensky NE, Criqui MH, Wright MC, Wassel CL, Brody SA and Allison MA: Blood pressure and vascular calcification. Hypertension. 55:990–997. 2010. View Article : Google Scholar : PubMed/NCBI

43 

Gudipaty SA, Lindblom J, Loftus PD, Redd MJ, Edes K, Davey CF, Krishnegowda V and Rosenblatt J: Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature. 543:118–121. 2017. View Article : Google Scholar : PubMed/NCBI

44 

Wang S, Li W, Zhang P, Wang Z, Ma X, Liu C, Vasilev K, Zhang L, Zhou X, Liu L, et al: Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx. J Adv Res. 41:63–75. 2022. View Article : Google Scholar : PubMed/NCBI

45 

Martinon F, Burns K and Tschopp J: The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 10:417–426. 2002. View Article : Google Scholar : PubMed/NCBI

46 

Pan X, Xu H, Ding Z, Luo S, Li Z, Wan R, Jiang J, Chen X, Liu S, Chen Z, et al: Guizhitongluo Tablet inhibits atherosclerosis and foam cell formation through regulating Piezo1/NLRP3 mediated macrophage pyroptosis. Phytomedicine. 132:1558272024. View Article : Google Scholar : PubMed/NCBI

47 

Proudfoot D, Skepper JN, Hegyi L, Bennett MR, Shanahan CM and Weissberg PL: Apoptosis regulates human vascular calcification in vitro: Evidence for initiation of vascular calcification by apoptotic bodies. Circ Res. 87:1055–1062. 2000. View Article : Google Scholar : PubMed/NCBI

48 

Clarke MCH, Littlewood TD, Figg N, Maguire JJ, Davenport AP, Goddard M and Bennett MR: Chronic apoptosis of vascular smooth muscle cells accelerates atherosclerosis and promotes calcification and medial degeneration. Circ Res. 102:1529–1538. 2008. View Article : Google Scholar : PubMed/NCBI

49 

Di C, Ji M, Li W, Liu X, Gurung R, Qin B, Ye S and Qi R: Pyroptosis of vascular smooth muscle cells as a potential new target for preventing vascular diseases. Cardiovasc Drugs Ther. Jun 1–2024.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI

50 

Okada K, Naito AT, Higo T, Nakagawa A, Shibamoto M, Sakai T, Hashimoto A, Kuramoto Y, Sumida T, Nomura S, et al: Wnt/β-catenin signaling contributes to skeletal myopathy in heart failure via direct interaction with forkhead Box O. Circ Heart Fail. 8:799–808. 2015. View Article : Google Scholar : PubMed/NCBI

51 

Zhang X, Leng S, Liu X, Hu X, Liu Y, Li X, Feng Q, Guo W, Li N, Sheng Z, et al: Ion channel Piezo1 activation aggravates the endothelial dysfunction under a high glucose environment. Cardiovasc Diabetol. 23:1502024. View Article : Google Scholar : PubMed/NCBI

52 

Cui S, Li Y, Zhang X, Wu B, Li M, Gao J, Xia H and Xu L: FGF5 protects heart from sepsis injury by attenuating cardiomyocyte pyroptosis through inhibiting CaMKII/NFκB signaling. Biochem Biophys Res Commun. 636:104–112. 2022. View Article : Google Scholar : PubMed/NCBI

53 

Li Y, Ahrens MJ, Wu A, Liu J and Dudley AT: Calcium/calmodulin-dependent protein kinase II activity regulates the proliferative potential of growth plate chondrocytes. Development. 138:359–370. 2011. View Article : Google Scholar :

54 

Yu L, Ma X, Sun J, Tong J, Shi L, Sun L and Zhang J: Fluid shear stress induces osteoblast differentiation and arrests the cell cycle at the G0 phase via the ERK1/2 pathway. Mol Med Rep. 16:8699–8708. 2017. View Article : Google Scholar : PubMed/NCBI

55 

Yang L, Dai R, Wu H, Cai Z, Xie N, Zhang X, Shen Y, Gong Z, Jia Y, Yu F, et al: Unspliced XBP1 counteracts β-catenin to inhibit vascular calcification. Circ Res. 130:213–229. 2022. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tao J, You D, Feng Z, Li H, Zhang Y, Cui Y, Lin K, Luo B, Yin S, Tan H, Tan H, et al: Mechanosensor Piezo1‑mediated smooth muscular cell pyroptosis contributes to vascular calcification. Int J Mol Med 56: 196, 2025.
APA
Tao, J., You, D., Feng, Z., Li, H., Zhang, Y., Cui, Y. ... Tan, H. (2025). Mechanosensor Piezo1‑mediated smooth muscular cell pyroptosis contributes to vascular calcification. International Journal of Molecular Medicine, 56, 196. https://doi.org/10.3892/ijmm.2025.5637
MLA
Tao, J., You, D., Feng, Z., Li, H., Zhang, Y., Cui, Y., Lin, K., Luo, B., Yin, S., Tan, H."Mechanosensor Piezo1‑mediated smooth muscular cell pyroptosis contributes to vascular calcification". International Journal of Molecular Medicine 56.5 (2025): 196.
Chicago
Tao, J., You, D., Feng, Z., Li, H., Zhang, Y., Cui, Y., Lin, K., Luo, B., Yin, S., Tan, H."Mechanosensor Piezo1‑mediated smooth muscular cell pyroptosis contributes to vascular calcification". International Journal of Molecular Medicine 56, no. 5 (2025): 196. https://doi.org/10.3892/ijmm.2025.5637
Copy and paste a formatted citation
x
Spandidos Publications style
Tao J, You D, Feng Z, Li H, Zhang Y, Cui Y, Lin K, Luo B, Yin S, Tan H, Tan H, et al: Mechanosensor Piezo1‑mediated smooth muscular cell pyroptosis contributes to vascular calcification. Int J Mol Med 56: 196, 2025.
APA
Tao, J., You, D., Feng, Z., Li, H., Zhang, Y., Cui, Y. ... Tan, H. (2025). Mechanosensor Piezo1‑mediated smooth muscular cell pyroptosis contributes to vascular calcification. International Journal of Molecular Medicine, 56, 196. https://doi.org/10.3892/ijmm.2025.5637
MLA
Tao, J., You, D., Feng, Z., Li, H., Zhang, Y., Cui, Y., Lin, K., Luo, B., Yin, S., Tan, H."Mechanosensor Piezo1‑mediated smooth muscular cell pyroptosis contributes to vascular calcification". International Journal of Molecular Medicine 56.5 (2025): 196.
Chicago
Tao, J., You, D., Feng, Z., Li, H., Zhang, Y., Cui, Y., Lin, K., Luo, B., Yin, S., Tan, H."Mechanosensor Piezo1‑mediated smooth muscular cell pyroptosis contributes to vascular calcification". International Journal of Molecular Medicine 56, no. 5 (2025): 196. https://doi.org/10.3892/ijmm.2025.5637
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team