Apoptosis in myocarditis and dilated cardiomyopathy: Does enterovirus genome persistence protect from apoptosis? — An endomyocardial biopsy study

Alter, Peter; Jobmann, M.; Meyer, Ellen; Pankuweit, Sabine; Maisch, Bernhard

doi:10.1016/s1054-8807(01)00077-1

Cited by 36 publications

(22 citation statements)

References 36 publications

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“…IB␣ may thus act as a host sensor for viral infection. Coxsackievirus and other Picornaviruses cause apoptosis of infected cells in vivo and in vitro (12)(13)(14)(15)(16)(17). Although expression of individual enterovirus polypeptides can cause apoptosis in vitro, it is unclear precisely how these viral polypeptides cause apoptosis (18)(19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Viral protease cleavage of inhibitor of κBα triggers host cell apoptosis

Zaragoza

Saura

Padalko

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Apoptosis is an innate immune response to viral infection that limits viral replication. However, the mechanisms by which cells detect viral infection and activate apoptosis are not completely understood. We now show that during Coxsackievirus infection, the viral protease 3C pro cleaves inhibitor of B␣ (IB␣). A proteolytic fragment of IB␣ then forms a stable complex with NF-B, translocates to the nucleus, and inhibits NF-B transactivation, increasing apoptosis and decreasing viral replication. In contrast, cells with reduced IB␣ expression are more susceptible to viral infection, with less apoptosis and more viral replication. IB␣ thus acts as a sensor of viral infection. Cleavage of host proteins by pathogen proteases is a novel mechanism by which the host recognizes and responds to viral infection.Coxsackievirus ͉ nitric oxide ͉ Picornavirus

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Section: Discussionmentioning

confidence: 99%

Viral protease cleavage of inhibitor of κBα triggers host cell apoptosis

Zaragoza

Saura

Padalko

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…An increased number of apoptotic cells have been described in the heart of patients with myocarditis (74). Consequently, molecular imaging of apoptosis should be valuable for the diagnosis of myocarditis and potentially for risk stratification and prognosis.…”

Section: Evaluation Of Known or Suspected Cardiomyopathymentioning

confidence: 99%

Hybrid PET/MR Imaging of the Heart: Potential, Initial Experiences, and Future Prospects

et al. 2013

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Learning Objectives: On successful completion of this activity, participants should be able to describe (1) advantages and shortcomings of hybrid PET/MR scanners with respect to cardiovascular applications (e.g. myocardial perfusion imaging and viability imaging), (2) additional value of the MR component in cardiac imaging, and (3) technical challenges and workflow considerations regarding hybrid PET/MR scanners in the field of cardiology (e.g. attenuation correction and cardiac/respiratory/patient motion).Financial Disclosure: Dr. Schwaiger is an investigator, meeting participant, and lecturer for Siemens Medical. The authors of this article have indicated no other relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, participants can access this activity through the SNMMI Web site (http:// www.snmmi.org/ce_online) through March 2016.PET/CT and other combined scanners have in the past decade rapidly emerged as important research tools and are proving to be invaluable for improved diagnostics in routine nuclear medicine. The design of hybrid PET/MR scanners presented a formidable technical challenge, and only recently were these instruments introduced to the market. Initial expectations of the performance of these scanners have been high, notably because of the potential for superior tissue contrast inherent in the MR modality, as well as the potential for multiparametric functional imaging in conjunction with PET. However, the additional value and potential clinical role that these new systems might bring to the cardiac field have yet to be documented. This review presents a comparative summary of the existing applications for PET and MR in the field of cardiology and suggests potential cardiac applications exploiting unique properties of the newly introduced combined instrumentation. The diverse range of imaging modalities for cardiology includes echocardiography, CT, MR imaging, SPECT, and PET, each of which offers distinct properties and advantages. The demand for combined PET/CT instrumentation in clinical nuclear medicine has grown remarkably, because of the notable advantages presented by hybrid imaging with respect to anatomic localization of lesions. Although these advantages were initially driven by the demands of oncology imaging, the resultant broader availability of PET/CT has provided the opportunity to use these scanners for indications beyond oncology, such as in the field of cardiac imaging (1). Furthermore, CT images are necessary for rapid attenuation correction, which is of particular importance for quantification in myocardial perfusion imaging. Through the use of suitable CT components a...

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“…Apoptosis of cardiac myocytes in vitro has also been demonstrated in response to serum and glucose deprivation (components of ischemia in vivo) (3) as well as during cardiac myocyte differentiation (37). Although there have been sporadic reports suggesting the importance of apoptosis in the pathogenesis of viral myocarditis (1,11,13,14,61,63), this mechanism of cellular death has not previously been extensively characterized for models of viral myocarditis.…”

Section: Two Pharmacologic Agents That Broadly Inhibit Caspase Activimentioning

confidence: 99%

Caspase Inhibition Protects against Reovirus-Induced Myocardial Injury In Vitro and In Vivo

DeBiasi

Robinson²,

Sherry

et al. 2004

J Virol

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Viral myocarditis is a disease with a high morbidity and mortality. The pathogenesis of this disease remains poorly characterized, with components of both direct virus-mediated and secondary inflammatory and immune responses contributing to disease. Apoptosis has increasingly been viewed as an important mechanism of myocardial injury in noninfectious models of cardiac disease, including ischemia and failure. Using a reovirus murine model of viral myocarditis, we characterized and targeted apoptosis as a key mechanism of virusassociated myocardial injury in vitro and in vivo. We demonstrated caspase-3 activation, in conjunction with terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling and annexin binding, in cardiac myocytes after myocarditic viral infection in vitro. We also demonstrated a tight temporal and geographical correlation between caspase-3 activation, histologic injury, and viral load in cardiac tissue after myocarditic viral infection in vivo. Two pharmacologic agents that broadly inhibit caspase activity, Q-VD-OPH and Z-VAD(OMe)-FMK, effectively inhibited virus-induced cellular death in vitro. The inhibition of caspase activity in vivo by the use of pharmacologic agents as well as genetic manipulation reduced virus-induced myocardial injury by 40 to 60% and dramatically improved survival in infected caspase-3-deficient animals. This study indicates that apoptosis plays a critical role in mediating cardiac injury in the setting of viral myocarditis and is the first demonstration that caspase inhibition may serve as a novel therapeutic strategy for this devastating disease.

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Apoptosis in myocarditis and dilated cardiomyopathy: Does enterovirus genome persistence protect from apoptosis? — An endomyocardial biopsy study

Cited by 36 publications

References 36 publications

Viral protease cleavage of inhibitor of κBα triggers host cell apoptosis

Viral protease cleavage of inhibitor of κBα triggers host cell apoptosis

Hybrid PET/MR Imaging of the Heart: Potential, Initial Experiences, and Future Prospects

Caspase Inhibition Protects against Reovirus-Induced Myocardial Injury In Vitro and In Vivo

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