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Carvedilol Diminishes Cardiac Remodeling Induced by High-Fructose/High-Fat Diet in Mice via Enhancing Cardiac β-Arrestin2 Signaling.
- Source :
-
Journal of cardiovascular pharmacology and therapeutics [J Cardiovasc Pharmacol Ther] 2020 Jul; Vol. 25 (4), pp. 354-363. Date of Electronic Publication: 2020 Feb 13. - Publication Year :
- 2020
-
Abstract
- Background: Insulin resistance (IR) is a well-known risk factor for cardiovascular complications. This study aimed to investigate the effect of a dietary model of IR in mice on cardiac remodeling, cardiac β-arrestin2 signaling, and the protective effects of carvedilol as a β-arrestin-biased agonist.<br />Methods and Results: Insulin resistance was induced by feeding mice high-fructose/high-fat diet (HFrHFD) for 16 weeks. Carvedilol was adiministered for 4 weeks starting at week 13. At the end of the experiment, body weight, heart weight, left and right ventricular thickness, visceral fat weight, fasting blood glucose (FBG), serum insulin, IR index, and serum endothelin-1 were measured. In addition, cardiac tissue samples were histopathologically examined. Also, cardiac levels of cardiotrophin-1, β-arrestin2, phosphatidylinositol 4,5 bisphosphate (PIP2), diacylglycerol (DAG), and phosphoserine 473 Akt (pS473 Akt) were measured. Results showed significant increases in the FBG, serum insulin, IR index, serum endothelin-1, cardiac DAG, cardiac fibrosis, and degenerated cardiac myofibrils in HFrHFD-fed mice associated with a significant reduction in cardiac levels of cardiotrophin-1, β-arrestin2, PIP2, and pS473 Akt. On the other hand, carvedilol significantly reduced the heart weight, FBG, serum insulin, IR index, serum endothelin-1, cardiac DAG, left ventricular thickness, right ventricular fibrosis, and degeneration of cardiac myofibrils. In addition, carvedilol significantly increased cardiac levels of cardiotrophin-1, β-arrestin2, PIP2, and pS473 Akt.<br />Conclusion: Carvedilol enhances cardiac β-arrestin2 signaling and reduces cardiac remodeling in HFrHFD-fed mice.
- Subjects :
- Animals
Cardiomegaly etiology
Cardiomegaly metabolism
Cardiomegaly physiopathology
Cytokines metabolism
Diet, High-Fat
Dietary Sugars
Disease Models, Animal
Fibrosis
Fructose
Male
Mice
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
Phosphatidylinositol 4,5-Diphosphate metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction
Ventricular Remodeling drug effects
beta-Arrestin 2 metabolism
Cardiomegaly prevention & control
Carvedilol pharmacology
Insulin Resistance
Myocytes, Cardiac drug effects
Ventricular Function, Left drug effects
Ventricular Function, Right drug effects
beta-Arrestin 2 agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1940-4034
- Volume :
- 25
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of cardiovascular pharmacology and therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 32052660
- Full Text :
- https://doi.org/10.1177/1074248420905683