Methamphetamine induces cardiomyopathy through GATA4/NF-κB/SASP axis-mediated cellular senescence
Abstract
With the world pandemic of methamphetamine (METH), METH-associated cardiomyopathy (MAC) has become a widespread epidemic and is also recognized as a cause of heart failure in young people. The mechanism of occurrence and development of MAC is not clear. In this study, firstly, the animal model was evaluated by echocardiography and myocardial pathological staining. The results revealed that the animal model exhibited cardiac injury consistent with clinical alterations of MAC, and the mice developed cardiac hypertrophy and fibrosis remodeling, which led to systolic dysfunction and left ventricular ejection fraction (%LVEF) < 40%. The expression of cellular senescence marker proteins (p16 and p21) and senescence-associated secretory phenotype (SASP) was significantly increased in mouse myocardial tissue. Secondly, mRNA sequencing analysis of cardiac tissues revealed the key molecule GATA4, and Western blot, qPCR and immunofluorescence results showed that the expression level of GATA4 was significantly increased after METH exposure. Finally, knockdown of GATA4 expression in H9C2 cells in vitro significantly attenuated METH-induced cardiomyocyte senescence. Consequently, METH causes cardiomyopathy through cellular senescence mediated by the GATA4/NF-κB/SASP axis, which is a feasible target for the treatment of MAC.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Aβ1-42-treated astrocytes have elevated expression levels of p16.
“In line with this, Western blot analysis revealed elevated expression levels of p16, a marker of cellular senescence [29], in astrocytes treated with Aβ1–42 (Figure 2C,D).”
From Aerobic exercise improves astrocyte mitochondrial quality and transfer to neurons in a mouse model of Alzheimer's disease (2025) · cites this paper as [29]
Cites
Length-independent telomere damage drives post-mitotic cardiomyocyte senescence
Anderson, R., Lagnado, A., Maggiorani, D., Walaszczyk, A., Dookun, E., Chapman, J., Birch, J., Salmonowicz, H., Ogrodnik, M., Jurk, D., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100492 · Cited by 532 · see citing works
Le, O. N. L., Rodier, F., Fontaine, F., Coppe, J., Campisi, J., DeGregori, J., Laverdière, C., Kokta, V., Haddad, E., & Beauséjour, C. M. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00567.x · Cited by 168 · see citing works
The relationship between crystalline methamphetamine use and methamphetamine dependence
McKetin, R., Kelly, E., & McLaren, J. (2006) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2006.04.007 · Cited by 145 · see citing works
Ageing, the autonomic nervous system and arrhythmia: From brain to heart
Chadda, K. R., Ajijola, O. A., Vaseghi, M., Shivkumar, K., Huang, C. L.-H., & Jeevaratnam, K. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.09.005 · Cited by 77 · see citing works
Yu, C., Narasipura, S. D., Richards, M. H., Hu, X., Yamamoto, B., & Al‐Harthi, L. (2017) · Aging Cell · doi:10.1111/acel.12593 · Cited by 57 · see citing works
Morin, D., Long, R., Panel, M., Laure, L., Taranu, A., Gueguen, C., Pons, S., Leoni, V., Caccia, C., Vatner, S. F., et al. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.04.035 · Cited by 24 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cai, J., Chen, Y., She, Y., He, X., Feng, H., Sun, H., Yin, M., Gao, J., Sheng, C., Li, Q., et al. (2025) · Brain Pathology · doi:10.1111/bpa.13316 · Cited by 30 · see citing works
- Authors
- Zhao, X., Lu, J., Zhang, C., Chen, C., Zhang, M., Zhang, J., Du, Q., & Wang, H.
- Affiliations
- Southern Medical University (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Du, Qingfeng
- Wang, Huijun
- Venue
- Toxicology and Applied Pharmacology
- Publisher
- Elsevier BV
- Published
- 2023-05
- Volume
- 466
- Pages
- 116457
- ISSN
- 0041-008X (ISSN-L)
- OpenAlex
- W4323922505
- Cited by
- 12
- References
- 6
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 4
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Toxicology and Applied Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- methamphetamine, cardiomyopathy, cellular senescence, senescence-associated secretory phenotype, GATA4, NF-κB, cardiac hypertrophy, myocardial fibrosis, systolic dysfunction, p16, p21, cardiomyocyte senescence, H9c2 cells
- MeSH terms
- Animals, Methamphetamine, Cardiomyopathies, Stroke Volume, Ventricular Function, Left, NF-kappa B, Cellular Senescence, Myocytes, Cardiac, GATA4 Transcription Factor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
