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HMG-CoA Reductase Inhibitor, Simvastatin Is Effective in Decreasing Degree of Myocarditis by Inhibiting Metalloproteinases Activation.
- Source :
-
Biomolecules [Biomolecules] 2021 Sep 28; Vol. 11 (10). Date of Electronic Publication: 2021 Sep 28. - Publication Year :
- 2021
-
Abstract
- Background: Acute myocarditis often progresses to heart failure because there is no effective, etiology-targeted therapy of this disease. Simvastatin has been shown to be cardioprotective by decreasing matrix metalloproteinases' (MMPs) activity. The study was designed to determine whether simvastatin inhibits MMPs activity, decreases the severity of inflammation and contractile dysfunction of the heart in experimental autoimmune myocarditis (EAM).<br />Methods: Simvastatin (3 or 30 mg/kg/day) was given to experimental rats with EAM by gastric gavage for 21 days. Then transthoracic echocardiography was performed, MMPs activity and troponin I level were determined and tissue samples were assessed under a light and transmission electron microscope.<br />Results: Hearts treated with simvastatin did not show left ventricular enlargement. As a result of EAM, there was an enhanced activation of MMP-9, which was significantly reduced in the high-dose simvastatin group compared to the low-dose group. It was accompanied by prevention of myofilaments degradation and reduction of severity of inflammation.<br />Conclusions: The cardioprotective effects of simvastatin in the acute phase of EAM are, at least in part, due to its ability to decrease MMP-9 activity and subsequent decline in myofilaments degradation and suppression of inflammation. These effects were achieved in doses equivalent to therapeutic doses in humans.
- Subjects :
- Animals
Autoimmune Diseases drug therapy
Autoimmune Diseases genetics
Autoimmune Diseases immunology
Cardiotonic Agents pharmacology
Echocardiography
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology
Inflammation genetics
Inflammation immunology
Inflammation pathology
Metalloproteases antagonists & inhibitors
Models, Animal
Myocarditis genetics
Myocarditis immunology
Myocarditis pathology
Rats
Ventricular Dysfunction, Left drug therapy
Ventricular Dysfunction, Left pathology
Ventricular Dysfunction, Left prevention & control
Inflammation drug therapy
Metalloproteases genetics
Myocarditis drug therapy
Simvastatin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2218-273X
- Volume :
- 11
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Biomolecules
- Publication Type :
- Academic Journal
- Accession number :
- 34680049
- Full Text :
- https://doi.org/10.3390/biom11101415