Cardiomyocyte apoptosis after antiviral WIN 54954 treatment in murine coxsackievirus B3 myocarditis. 2002

Ville Kytö, and Antti Saraste, and Jan Fohlman, and Nils-G Ilbäck, and Heli Harvala, and Tytti Vuorinen, and Timo Hyypiä
Department of Anatomy, University of Turku, Turku, Finland. ville.kyto@utu.fi

OBJECTIVE Cardiomyocyte apoptosis (CA) is known to occur in experimental coxsackievirus B3 (CVB3) myocarditis. However, the mechanisms of CA induction are not well known. In this study we investigate the role of direct viral induction of CA in CVB3 myocarditis. METHODS A/J mice were infected with the Woodruff strain of CVB3 and treated with WIN 54954 for 5 days thereafter. WIN 54954, a compound that inhibits early events of picornavirus infection, is known to dramatically reduce mortality in murine CVB3 myocarditis without abrogating systemic or myocardial inflammation. Presence of viral RNA (in situ hybridization), CA (TUNEL method) and histopathology were studied in transverse ventricular sections at day 7 post infection (n = 8 treated and n = 8 non-treated). RESULTS The proportion of cardiomyocytes containing viral RNA was 89% lower in WIN 54954 treated mice when compared with non-treated mice (0.29 +/- 0.56% vs 2.76 +/- 1.65%, p = 0.003). Treatment also reduced the amount of CA by 52% compared with non-treated mice (0.20 +/- 0.06% vs 0.42 +/- 0.06%, p < 0.001). The reduction of CA by WIN treatment did not result in any increase of necrosis, in fact treatment reduced the area of necrotic lesions by 77% (2.51 +/- 1.64% vs 11.10 +/- 8.76%, p = 0.028). CONCLUSIONS Taking the results of the reduced CA, necrosis and viral RNA with no effect on inflammation into account, our findings suggest the importance of direct viral effect in cardiomyocyte damage by both apoptosis and necrosis in CVB3 myocarditis.

UI MeSH Term Description Entries
D007555 Isoxazoles Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions. Isoxazole
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009205 Myocarditis Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies. Carditis,Myocarditides
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D009336 Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.
D004769 Enterovirus Infections Diseases caused by ENTEROVIRUS. Infections, Enterovirus,Enterovirus Infection,Infection, Enterovirus
D006352 Heart Ventricles The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation. Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis

Related Publications

Ville Kytö, and Antti Saraste, and Jan Fohlman, and Nils-G Ilbäck, and Heli Harvala, and Tytti Vuorinen, and Timo Hyypiä
November 1996, Circulation,
Ville Kytö, and Antti Saraste, and Jan Fohlman, and Nils-G Ilbäck, and Heli Harvala, and Tytti Vuorinen, and Timo Hyypiä
March 2007, Journal of Asian natural products research,
Ville Kytö, and Antti Saraste, and Jan Fohlman, and Nils-G Ilbäck, and Heli Harvala, and Tytti Vuorinen, and Timo Hyypiä
February 1992, Antimicrobial agents and chemotherapy,
Ville Kytö, and Antti Saraste, and Jan Fohlman, and Nils-G Ilbäck, and Heli Harvala, and Tytti Vuorinen, and Timo Hyypiä
November 2019, Experimental animals,
Ville Kytö, and Antti Saraste, and Jan Fohlman, and Nils-G Ilbäck, and Heli Harvala, and Tytti Vuorinen, and Timo Hyypiä
January 1993, Scandinavian journal of infectious diseases. Supplementum,
Ville Kytö, and Antti Saraste, and Jan Fohlman, and Nils-G Ilbäck, and Heli Harvala, and Tytti Vuorinen, and Timo Hyypiä
February 2012, The Journal of infectious diseases,
Ville Kytö, and Antti Saraste, and Jan Fohlman, and Nils-G Ilbäck, and Heli Harvala, and Tytti Vuorinen, and Timo Hyypiä
October 1992, International journal of experimental pathology,
Ville Kytö, and Antti Saraste, and Jan Fohlman, and Nils-G Ilbäck, and Heli Harvala, and Tytti Vuorinen, and Timo Hyypiä
January 1992, Heart and vessels,
Ville Kytö, and Antti Saraste, and Jan Fohlman, and Nils-G Ilbäck, and Heli Harvala, and Tytti Vuorinen, and Timo Hyypiä
September 1983, Infection and immunity,
Ville Kytö, and Antti Saraste, and Jan Fohlman, and Nils-G Ilbäck, and Heli Harvala, and Tytti Vuorinen, and Timo Hyypiä
March 1996, Virus research,
Copied contents to your clipboard!