The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Leptin Induces Hypertrophy via Endothelin-1–Reactive Oxygen Species Pathway in Cultured Neonatal Rat Cardiomyocytes
Abstract
Background— Obesity is a major risk factor for the development of cardiovascular disease. Emerging evidence indicates that leptin, a protein encoded by the obesity gene, is linked with cardiac hypertrophy in obese humans and directly induces cardiomyocyte hypertrophy in vitro. However, the mechanisms by which leptin induces cardiomyocyte hypertrophy are poorly understood. Methods and Results— This study investigated how leptin contributes to cardiomyocyte hypertrophy. Cultured neonatal rat cardiomyocytes were used to evaluate the effects of leptin on hypertrophy. Both endothelin-1 (ET-1) and reactive oxygen species (ROS) levels were elevated in a concentration-dependent manner in cardiomyocytes treated with leptin for 4 hours compared with those cells without leptin treatment. ET-1 stimulated ROS production in a concentration-dependent manner in cardiomyocytes. The augmentation of ROS levels in cardiomyocytes treated with both leptin and ET-1 was reversed by a selective ET A receptor antagonist, ABT-627, and catalase, a hydrogen peroxide–decomposing enzyme. After treatment for 72 hours, leptin or ET-1 concentration-dependently increased total RNA levels, cell surface areas, and protein synthesis in cardiomyocytes, all of which were significantly inhibited by ABT-627 or catalase treatment. Conclusions— These findings indicate that leptin elevates ET-1 and ROS levels, resulting in hypertrophy of cultured neonatal rat cardiac myocytes. The ET-1–ET A –ROS pathway may be involved in cardiomyocyte hypertrophy induced by leptin. ET A receptor antagonists and antioxidant therapy may provide an effective means of ameliorating cardiac dysfunction in obese humans.
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“Leptin can also induce generation of reactive oxygen species in the heart (379).”
From Cardiac remodeling in obesity (2008) · cites this paper as [379]
In the citing paper
“Several reports have suggested that leptin directly induced hypertrophy in both human and rodent cardiomyocytes (217, 292, 293, 379).”
From Cardiac remodeling in obesity (2008) · cites this paper as [379]
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Metadata
- Authors
- Xu, F.-P., Chen, M.-S., Wang, Y.-Z., Yi, Q., Lin, S.-B., Chen, A. F., & Luo, J.-D.
- Affiliations
- From the Departments of Pharmacology (F.-P.X., Q.Y., S.-B.L., J.-D.L.) and Internal Medicine (M.-S.C.), Guangzhou Medical College, Guangzhou, China; the Department of Research Laboratory of Pathophysiology, PLA General Hospital, Beijing (Y.-Z.W.), China; and Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Mich (A.F.C., J.-D.L.). Dr Xu is now at the Department of Pathology, Preclinical Medicine School, Sun Yat-sen University, Guangzhou...
- Sun Yat-sen University (CN)
- ORCID
- Chen, Alex F.
- Venue
- Circulation
- Published
- 2004-09-07
- Volume
- 110
- Issue
- 10
- Pages
- 1269-1275
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2004341742
- Cited by
- 234
- References
- 44
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 12 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 7 · 2015: 9 · 2014: 8 · 2013: 6 · 2012: 13
- FWCI
- 14.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- leptin, cardiac hypertrophy, endothelin-1, reactive oxygen species, ETA receptor, atrasentan, catalase, neonatal rat cardiomyocytes, obesity, antioxidant therapy, obesity-related cardiovascular disease
- MeSH terms
- Atrasentan, Animals, Animals, Newborn, Antioxidants, Catalase, Cells, Cultured, Gene Expression Regulation, Cardiomegaly, Atrial Natriuretic Factor, Obesity, Pyrrolidines, RNA, Messenger, Rats, Sprague-Dawley, Reactive Oxygen Species, Oxidative Stress, Endothelin-1, Reverse Transcriptase Polymerase Chain Reaction, Leptin, Myocytes, Cardiac, Cell Size, Rats, Endothelin A Receptor Antagonists
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