» Articles » PMID: 21183501

Mesenchymal Stem Cells Improve Murine Acute Coxsackievirus B3-induced Myocarditis

Overview
Journal Eur Heart J
Date 2010 Dec 25
PMID 21183501
Citations 57
Authors
Affiliations
Soon will be listed here.
Abstract

Aims: Coxsackievirus B3 (CVB3)-induced myocarditis, initially considered a sole immune-mediated disease, also results from a direct CVB3-mediated injury of the cardiomyocytes. Mesenchymal stem cells (MSCs) have, besides immunomodulatory, also anti-apoptotic features. In view of clinical translation, we first analysed whether MSCs can be infected by CVB3. Next, we explored whether and how MSCs could reduce the direct CVB3-mediated cardiomyocyte injury and viral progeny release, in vitro, in the absence of immune cells. Finally, we investigated whether MSC application could improve murine acute CVB3-induced myocarditis.

Methods And Results: Phase contrast pictures and MTS viability assay demonstrated that MSCs did not suffer from CVB3 infection 4-12-24-48 h after CVB3 infection. Coxsackievirus B3 RNA copy number decreased in this time frame, suggesting that no CVB3 replication took place. Co-culture of MSCs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis, oxidative stress, intracellular viral particle production, and viral progeny release in a nitric oxide (NO)-dependent manner. Moreover, MSCs required priming via interferon-γ (IFN-γ) to exert their protective effects. In vivo, MSC application improved the contractility and relaxation parameters in CVB3-induced myocarditis, which was paralleled with a reduction in cardiac apoptosis, cardiomyocyte damage, left ventricular tumour necrosis factor-α mRNA expression, and cardiac mononuclear cell activation. Mesenchymal stem cells reduced the CVB3-induced CD4- and CD8- T cell activation in an NO-dependent way and required IFN-γ priming.

Conclusion: We conclude that MSCs improve murine acute CVB3-induced myocarditis via their anti-apoptotic and immunomodulatory properties, which occur in an NO-dependent manner and require priming via IFN-γ.

Citing Articles

Innate and adaptive immunity in acute myocarditis.

Golino M, Harding D, Del Buono M, Fanti S, Mohiddin S, Toldo S Int J Cardiol. 2024; 404:131901.

PMID: 38403204 PMC: 11450758. DOI: 10.1016/j.ijcard.2024.131901.


Sex- and age-related differences in the inflammatory properties of cardiac fibroblasts: impact on the cardiosplenic axis and cardiac fibrosis.

Pappritz K, Puhl S, Matz I, Brauer E, Shia Y, El-Shafeey M Front Cardiovasc Med. 2023; 10:1117419.

PMID: 38054090 PMC: 10694208. DOI: 10.3389/fcvm.2023.1117419.


Appendectomy Mitigates Coxsackievirus B3-Induced Viral Myocarditis.

Niu C, Xu W, Xiong S Viruses. 2023; 15(10).

PMID: 37896753 PMC: 10611117. DOI: 10.3390/v15101974.


Reconstituted Extracellular Vesicles from Human Platelets Decrease Viral Myocarditis in Mice.

Beetler D, Bruno K, Watkins M, Xu V, Chekuri I, Giresi P Small. 2023; 19(49):e2303317.

PMID: 37612820 PMC: 10840864. DOI: 10.1002/smll.202303317.


Designing a multi-epitope vaccine against coxsackievirus B based on immunoinformatics approaches.

Huang S, Zhang C, Li J, Dai Z, Huang J, Deng F Front Immunol. 2022; 13:933594.

PMID: 36439191 PMC: 9682020. DOI: 10.3389/fimmu.2022.933594.


References
1.
Schwarz K . Oxidative stress during viral infection: a review. Free Radic Biol Med. 1996; 21(5):641-9. DOI: 10.1016/0891-5849(96)00131-1. View

2.
Kasper G, Mao L, Geissler S, Draycheva A, Trippens J, Kuhnisch J . Insights into mesenchymal stem cell aging: involvement of antioxidant defense and actin cytoskeleton. Stem Cells. 2009; 27(6):1288-97. DOI: 10.1002/stem.49. View

3.
Halkos M, Zhao Z, Kerendi F, Wang N, Jiang R, Schmarkey L . Intravenous infusion of mesenchymal stem cells enhances regional perfusion and improves ventricular function in a porcine model of myocardial infarction. Basic Res Cardiol. 2008; 103(6):525-36. DOI: 10.1007/s00395-008-0741-0. View

4.
Bergelson J, Cunningham J, Droguett G, Krithivas A, Hong J, Horwitz M . Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science. 1997; 275(5304):1320-3. DOI: 10.1126/science.275.5304.1320. View

5.
Szelid Z, Pokreisz P, Liu X, Vermeersch P, Marsboom G, Gillijns H . Cardioselective nitric oxide synthase 3 gene transfer protects against myocardial reperfusion injury. Basic Res Cardiol. 2009; 105(2):169-79. DOI: 10.1007/s00395-009-0077-4. View