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Carvedilol Inhibits Matrix Metalloproteinase-2 Activation in Experimental Autoimmune Myocarditis: Possibilities of Cardioprotective Application.
J Cardiovasc Pharmacol Ther. 2018 Jan; 23(1):89-97.JC

Abstract

AIMS

Acute myocarditis is a potentially lethal inflammatory heart disease that frequently precedes the development of dilated cardiomyopathy and subsequent heart failure. At present, there is no effective standardized therapy for acute myocarditis, besides the optimal care of heart failure and arrhythmias in accordance with evidence-based guidelines and specific etiology-driven therapy for infectious myocarditis. Carvedilol has been shown to be cardioprotective by reducing cardiac pro-inflammatory cytokines present in oxidative stress in certain heart diseases. However, effects of carvedilol administration in acute myocarditis with its impact on matrix metalloproteinases' (MMPs) activation have not been elucidated.

METHODS AND RESULTS

Carvedilol in 3 doses (2, 10, and 30 mg/kg) was given daily to 3 study groups of rats (n = 8) with experimental autoimmune myocarditis by gastric gavage for 3 weeks. In comparison to untreated rats (n = 8) with induced myocarditis, carvedilol significantly prevented the left ventricle enlargement and/or systolic dysfunction depending on the dose in study groups. Performed zymography showed enhanced MMP-2 activity in untreated rats, while carvedilol administration reduced alterations. This was accompanied by prevention of troponin I release and myofilaments degradation in cardiac muscle tissue. Additionally, severe inflammatory cell infiltration was detected in the nontreated group. Carvedilol in all doses tested, had no impact on severity of inflammation. The severity of inflammation did not differ between study groups and in relation to the untreated group.

CONCLUSIONS

The protective effects of carvedilol on heart function observed in the acute phase of experimental autoimmune myocarditis seem to be associated with its ability to decrease MMP-2 activity and subsequently prevent degradation of myofilaments and release of troponin I while not related to suppression of inflammation.

Authors+Show Affiliations

1 Department of Pharmacology, Wroclaw Medical University, Wroclaw, Poland.2 Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland.3 Department of Medical Laboratory Diagnostics, Wroclaw Medical University, Wroclaw, Poland.4 Department of Epizootiology and Clinic of Bird and Exotic Animals, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.1 Department of Pharmacology, Wroclaw Medical University, Wroclaw, Poland.5 Department of Medical Biochemistry, Wroclaw Medical University, Wroclaw, Poland.3 Department of Medical Laboratory Diagnostics, Wroclaw Medical University, Wroclaw, Poland.6 Department of Clinical Pathomorphology, Poznan University of Medical Sciences, Poznan, Poland.2 Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland.2 Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland. 7 Department of Physiotherapy, University School of Physical Education, Wroclaw, Poland.2 Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland.1 Department of Pharmacology, Wroclaw Medical University, Wroclaw, Poland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28854816

Citation

Skrzypiec-Spring, Monika, et al. "Carvedilol Inhibits Matrix Metalloproteinase-2 Activation in Experimental Autoimmune Myocarditis: Possibilities of Cardioprotective Application." Journal of Cardiovascular Pharmacology and Therapeutics, vol. 23, no. 1, 2018, pp. 89-97.
Skrzypiec-Spring M, Haczkiewicz K, Sapa A, et al. Carvedilol Inhibits Matrix Metalloproteinase-2 Activation in Experimental Autoimmune Myocarditis: Possibilities of Cardioprotective Application. J Cardiovasc Pharmacol Ther. 2018;23(1):89-97.
Skrzypiec-Spring, M., Haczkiewicz, K., Sapa, A., Piasecki, T., Kwiatkowska, J., Ceremuga, I., Wozniak, M., Biczysko, W., Kobierzycki, C., Dziegiel, P., Podhorska-Okolow, M., & Szelag, A. (2018). Carvedilol Inhibits Matrix Metalloproteinase-2 Activation in Experimental Autoimmune Myocarditis: Possibilities of Cardioprotective Application. Journal of Cardiovascular Pharmacology and Therapeutics, 23(1), 89-97. https://doi.org/10.1177/1074248417725058
Skrzypiec-Spring M, et al. Carvedilol Inhibits Matrix Metalloproteinase-2 Activation in Experimental Autoimmune Myocarditis: Possibilities of Cardioprotective Application. J Cardiovasc Pharmacol Ther. 2018;23(1):89-97. PubMed PMID: 28854816.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carvedilol Inhibits Matrix Metalloproteinase-2 Activation in Experimental Autoimmune Myocarditis: Possibilities of Cardioprotective Application. AU - Skrzypiec-Spring,Monika, AU - Haczkiewicz,Katarzyna, AU - Sapa,Agnieszka, AU - Piasecki,Tomasz, AU - Kwiatkowska,Joanna, AU - Ceremuga,Ireneusz, AU - Wozniak,Mieczyslaw, AU - Biczysko,Wieslawa, AU - Kobierzycki,Christopher, AU - Dziegiel,Piotr, AU - Podhorska-Okolow,Marzenna, AU - Szelag,Adam, Y1 - 2017/08/31/ PY - 2017/9/1/pubmed PY - 2018/7/22/medline PY - 2017/9/1/entrez KW - acute myocarditis KW - autoimmune myocarditis KW - carvedilol KW - metalloproteinase-2 SP - 89 EP - 97 JF - Journal of cardiovascular pharmacology and therapeutics JO - J Cardiovasc Pharmacol Ther VL - 23 IS - 1 N2 - AIMS: Acute myocarditis is a potentially lethal inflammatory heart disease that frequently precedes the development of dilated cardiomyopathy and subsequent heart failure. At present, there is no effective standardized therapy for acute myocarditis, besides the optimal care of heart failure and arrhythmias in accordance with evidence-based guidelines and specific etiology-driven therapy for infectious myocarditis. Carvedilol has been shown to be cardioprotective by reducing cardiac pro-inflammatory cytokines present in oxidative stress in certain heart diseases. However, effects of carvedilol administration in acute myocarditis with its impact on matrix metalloproteinases' (MMPs) activation have not been elucidated. METHODS AND RESULTS: Carvedilol in 3 doses (2, 10, and 30 mg/kg) was given daily to 3 study groups of rats (n = 8) with experimental autoimmune myocarditis by gastric gavage for 3 weeks. In comparison to untreated rats (n = 8) with induced myocarditis, carvedilol significantly prevented the left ventricle enlargement and/or systolic dysfunction depending on the dose in study groups. Performed zymography showed enhanced MMP-2 activity in untreated rats, while carvedilol administration reduced alterations. This was accompanied by prevention of troponin I release and myofilaments degradation in cardiac muscle tissue. Additionally, severe inflammatory cell infiltration was detected in the nontreated group. Carvedilol in all doses tested, had no impact on severity of inflammation. The severity of inflammation did not differ between study groups and in relation to the untreated group. CONCLUSIONS: The protective effects of carvedilol on heart function observed in the acute phase of experimental autoimmune myocarditis seem to be associated with its ability to decrease MMP-2 activity and subsequently prevent degradation of myofilaments and release of troponin I while not related to suppression of inflammation. SN - 1940-4034 UR - https://www.unboundmedicine.com/medline/citation/28854816/Carvedilol_Inhibits_Matrix_Metalloproteinase_2_Activation_in_Experimental_Autoimmune_Myocarditis:_Possibilities_of_Cardioprotective_Application_ L2 - https://journals.sagepub.com/doi/10.1177/1074248417725058?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -