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Updated: Jun 18, 2026
A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats
Published on: December 2, 2016
Effect of targeting mitogen-activated protein kinase on cardiac remodeling in rats
Azza Baraka1, Maher Mikhail, Aida Guemei
1Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt. mnhbaraka@yahoo.com
Background:
Increasing evidence suggests that the activation of p38 mitogen-activated protein kinase (p38MAPK) plays a role in cardiac remodeling. Targeting p38MAPK using drugs reported to interfere with its phosphorylation, namely statins and all-trans retinoic acid (atRA), might play a role in ameliorating this remodeling.
Methods And Results:
Cardiac remodeling was induced in male albino rats by chronic inhibition of nitric oxide (NO) synthesis by N-nitro L-arginine methyl ester (L-NAME). Daily oral administration of L-NAME for 4 weeks resulted in the elevation of mean arterial blood pressure (MABP) together with cardiac remodeling evidenced by an increase in left ventricular-body weight ratio together with an increase in cardiac hydroxyproline concentration and a decrease in left ventricular papillary muscle-developed tension. An elevation in cardiac phosphorylated p38MAPK concentration, tumor necrosis factor alpha concentration and in cardiac caspase 3 activity was also observed. Administration of either rosuvastatin or all-trans retinoic acid (atRA), starting 4 weeks after L-NAME administration, ameliorated remodeling and improved all studied parameters.
Conclusions:
Targeting MAPK might represent a useful therapeutic avenue to ameliorate cardiac remodeling and support the notion that atRA and statins are potential candidates for the prevention and therapy of cardiac remodeling.
Insights
Statins and all-trans retinoic acid (atRA) show promise in treating cardiac remodeling by targeting p38 mitogen-activated protein kinase (p38MAPK). These drugs may offer a new therapeutic approach for preventing and managing heart conditions.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pharmacology
Background:
- Cardiac remodeling is increasingly linked to p38 mitogen-activated protein kinase (p38MAPK) activation.
- Statins and all-trans retinoic acid (atRA) are known to interfere with p38MAPK phosphorylation.
- These drugs may hold potential for mitigating cardiac remodeling processes.
Purpose of the Study:
- To investigate the therapeutic potential of statins and atRA in a rat model of cardiac remodeling.
- To evaluate the effects of these agents on cardiac structure, function, and molecular markers.
Main Methods:
- Cardiac remodeling was induced in rats using N-nitro L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthesis.
- Rats received daily oral administration of L-NAME for four weeks.
- Treatment with rosuvastatin or atRA was initiated after four weeks of L-NAME administration.
Main Results:
- L-NAME induced elevated blood pressure, cardiac remodeling (increased left ventricular-body weight ratio, hydroxyproline concentration), and impaired muscle function.
- Increased cardiac levels of phosphorylated p38MAPK, tumor necrosis factor alpha, and caspase 3 activity were observed.
- Rosuvastatin and atRA treatments significantly ameliorated cardiac remodeling and improved all measured parameters.
Conclusions:
- Targeting p38MAPK presents a viable therapeutic strategy for ameliorating cardiac remodeling.
- Statins and atRA demonstrate potential as therapeutic agents for the prevention and treatment of cardiac remodeling.
