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Carvedilol improves left ventricular function in murine coxsackievirus-induced acute myocarditis association with reduced myocardial interleukin-1beta and MMP-8 expression and a modulated immune response.
Eur J Heart Fail. 2005 Jun; 7(4):444-52.EJ

Abstract

BACKGROUND

Proinflammatory cytokines induce the expression of matrix metalloproteinases that play a crucial role in myocardial remodeling. Beta-adrenergic receptor stimulation influences the production of cytokines heralding the possibility of modulating cytokine production by beta-adrenergic blockers.

METHODS AND RESULTS

In a coxsackievirus B3 murine myocarditis model (BALB/c), effects of carvedilol and metoprolol on myocardial cytokine expression, inflammatory cell infiltration and MMP/TIMP profiles were investigated. In carvedilol-treated mice, a significant improvement in left ventricular function was documented 10 days post infection. In infected mice (n=10), IL-1beta, TNF-alpha, TGF-beta(1) and IL-10 myocardial mRNA abundance were increased significantly (240%, 200%, 161%, and 230%) compared to controls (n=10), while IL-15 mRNA was markedly reduced (70%). Infected mice showed significantly increased infiltrations with CD3-, CD4- and CD8-T-lymphocytes (730%, 1110%, 380%). In the infected mice, myocardial MMP/TIMP profiles presented a significant upregulation of membrane type-1 MMP, MMP-9, MMP-8 and MMP-3 (150%, 160%, 340%, and 270%) and a significant decrease in TIMP-4 levels (75%). Carvedilol attenuated over-expression of myocardial TGF-beta(1), IL-1beta and MMP-8 mRNA expression significantly and induced a relevant IL-10 mRNA expression in the infected mice (n=10). By an unchanged infiltration with CD3-T-lymphocytes, carvedilol showed a representative reduction in CD4-T-lymphocytes.

CONCLUSION

Carvedilol treatment in experimental myocarditis leads to reduced expression of proinflammatory cytokines and MMPs, which contributes to reduced matrix degradation and ultimately to improved structural integrity of the heart. Besides the antiadrenergic potential, carvedilol is beneficial due to a wide range of biological activities (antiinflammatory, antifibrotic, antioxidative and immunomodulatory).

Authors+Show Affiliations

Department of Internal Medicine II, Cardiology and Pneumonology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany. pauschinger@ukbf.fu-berlin.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15921778

Citation

Pauschinger, Matthias, et al. "Carvedilol Improves Left Ventricular Function in Murine Coxsackievirus-induced Acute Myocarditis Association With Reduced Myocardial Interleukin-1beta and MMP-8 Expression and a Modulated Immune Response." European Journal of Heart Failure, vol. 7, no. 4, 2005, pp. 444-52.
Pauschinger M, Rutschow S, Chandrasekharan K, et al. Carvedilol improves left ventricular function in murine coxsackievirus-induced acute myocarditis association with reduced myocardial interleukin-1beta and MMP-8 expression and a modulated immune response. Eur J Heart Fail. 2005;7(4):444-52.
Pauschinger, M., Rutschow, S., Chandrasekharan, K., Westermann, D., Weitz, A., Peter Schwimmbeck, L., Zeichhardt, H., Poller, W., Noutsias, M., Li, J., Schultheiss, H. P., & Tschope, C. (2005). Carvedilol improves left ventricular function in murine coxsackievirus-induced acute myocarditis association with reduced myocardial interleukin-1beta and MMP-8 expression and a modulated immune response. European Journal of Heart Failure, 7(4), 444-52.
Pauschinger M, et al. Carvedilol Improves Left Ventricular Function in Murine Coxsackievirus-induced Acute Myocarditis Association With Reduced Myocardial Interleukin-1beta and MMP-8 Expression and a Modulated Immune Response. Eur J Heart Fail. 2005;7(4):444-52. PubMed PMID: 15921778.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carvedilol improves left ventricular function in murine coxsackievirus-induced acute myocarditis association with reduced myocardial interleukin-1beta and MMP-8 expression and a modulated immune response. AU - Pauschinger,Matthias, AU - Rutschow,Susanne, AU - Chandrasekharan,Kumaran, AU - Westermann,Dirk, AU - Weitz,Anneke, AU - Peter Schwimmbeck,Lothar, AU - Zeichhardt,Heinz, AU - Poller,Wolfgang, AU - Noutsias,Michel, AU - Li,Jun, AU - Schultheiss,Heinz-Peter, AU - Tschope,Carsten, PY - 2003/11/07/received PY - 2004/05/17/revised PY - 2004/07/05/accepted PY - 2005/6/1/pubmed PY - 2005/9/28/medline PY - 2005/6/1/entrez SP - 444 EP - 52 JF - European journal of heart failure JO - Eur J Heart Fail VL - 7 IS - 4 N2 - BACKGROUND: Proinflammatory cytokines induce the expression of matrix metalloproteinases that play a crucial role in myocardial remodeling. Beta-adrenergic receptor stimulation influences the production of cytokines heralding the possibility of modulating cytokine production by beta-adrenergic blockers. METHODS AND RESULTS: In a coxsackievirus B3 murine myocarditis model (BALB/c), effects of carvedilol and metoprolol on myocardial cytokine expression, inflammatory cell infiltration and MMP/TIMP profiles were investigated. In carvedilol-treated mice, a significant improvement in left ventricular function was documented 10 days post infection. In infected mice (n=10), IL-1beta, TNF-alpha, TGF-beta(1) and IL-10 myocardial mRNA abundance were increased significantly (240%, 200%, 161%, and 230%) compared to controls (n=10), while IL-15 mRNA was markedly reduced (70%). Infected mice showed significantly increased infiltrations with CD3-, CD4- and CD8-T-lymphocytes (730%, 1110%, 380%). In the infected mice, myocardial MMP/TIMP profiles presented a significant upregulation of membrane type-1 MMP, MMP-9, MMP-8 and MMP-3 (150%, 160%, 340%, and 270%) and a significant decrease in TIMP-4 levels (75%). Carvedilol attenuated over-expression of myocardial TGF-beta(1), IL-1beta and MMP-8 mRNA expression significantly and induced a relevant IL-10 mRNA expression in the infected mice (n=10). By an unchanged infiltration with CD3-T-lymphocytes, carvedilol showed a representative reduction in CD4-T-lymphocytes. CONCLUSION: Carvedilol treatment in experimental myocarditis leads to reduced expression of proinflammatory cytokines and MMPs, which contributes to reduced matrix degradation and ultimately to improved structural integrity of the heart. Besides the antiadrenergic potential, carvedilol is beneficial due to a wide range of biological activities (antiinflammatory, antifibrotic, antioxidative and immunomodulatory). SN - 1388-9842 UR - https://www.unboundmedicine.com/medline/citation/15921778/Carvedilol_improves_left_ventricular_function_in_murine_coxsackievirus_induced_acute_myocarditis_association_with_reduced_myocardial_interleukin_1beta_and_MMP_8_expression_and_a_modulated_immune_response_ L2 - https://doi.org/10.1016/j.ejheart.2004.07.002 DB - PRIME DP - Unbound Medicine ER -