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Molecular Mechanisms behind Persistent Presence of Parvovirus B19 in Human Dilated Myocardium
Daiva Bironaitė1, Ieva Kažukauskienė2, Julius Bogomolovas3
1Department of Regenerative Medicine, State Research Institute Center for Innovative Medicine, Vilnius, Lithuania. daibironai@gmail.com.
Abstract:
The role of parvovirus B19 (PVB19) in the pathogenesis of idiopathic dilated cardiomyopathy (DCM) remains poorly understood. Therefore, we have measured the levels of inflammation, fibrosis, apoptosis, and necrosis in endomyocardial biopsies (EMBs) and sera of nonischemic PVB19-positive (n = 14) and PVB19-negative (n = 18) DCM patients. Chronic persistence of PVB19 in myocardium did not induce significant infiltration of T cells (CD3 and CD45Ro) and macrophages (CD68), and did not secrete TNFα, IL-6, and CRB. The fibrosis in PVB19-positive EMBs was also lower compared to the virus-negative ones, while ECM degrading matrix metalloproteinase MMP1 and gelatinase MMP2 were significantly (by twofold) upregulated. In addition, there was no activation of neither apoptotic nor necrotic pathways. However, levels of antiapoptotic mitochondrial Bcl-2 and heat shock protein 60 (Hsp60) in PVB19-positive biopsies were almost threefold lower than in PVB19-negative ones revealing impairment of mitochondria. Altogether, data indicate that persistence of PVB19 in myocardiums of nonischemic DCM patients can cause myocardial ECM remodeling through the MMPs, such as MMP1 and MMP2, and mitochondrial impairment. The correlative analysis of measured biomarkers suggested likely further activation of apoptotic cell death pathways rather than fibrosis. Data also suggest that antiviral therapy could be beneficial for PVB19-positive DCM patients by managing further pathological myocardial remodeling.
Insights
Parvovirus B19 (PVB19) persistence in dilated cardiomyopathy (DCM) patients impairs mitochondria and remodels the extracellular matrix (ECM) via matrix metalloproteinases (MMPs). Antiviral therapy may benefit PVB19-positive DCM patients.
Area of Science:
- Cardiology
- Virology
- Pathology
Background:
- The role of parvovirus B19 (PVB19) in idiopathic dilated cardiomyopathy (DCM) pathogenesis is unclear.
- PVB19 infection is a potential trigger for cardiac conditions.
Purpose of the Study:
- To investigate the impact of chronic PVB19 persistence on myocardial inflammation, fibrosis, apoptosis, and mitochondrial function in nonischemic DCM patients.
- To explore potential therapeutic strategies for PVB19-positive DCM.
Main Methods:
- Analysis of endomyocardial biopsies (EMBs) and sera from PVB19-positive and negative DCM patients.
- Measurement of inflammatory cell infiltration (CD3, CD45Ro, CD68), cytokine secretion (TNFα, IL-6), fibrosis, apoptosis markers, and mitochondrial proteins (Bcl-2, Hsp60).
- Assessed matrix metalloproteinases (MMPs) involved in extracellular matrix (ECM) degradation.
Main Results:
- Chronic PVB19 in myocardium did not increase inflammatory cell infiltration or pro-inflammatory cytokines.
- Fibrosis was lower in PVB19-positive EMBs, but ECM-degrading MMP1 and MMP2 were upregulated twofold.
- Mitochondrial impairment was indicated by a threefold decrease in antiapoptotic Bcl-2 and Hsp60 in PVB19-positive biopsies, with no significant apoptosis or necrosis activation.
Conclusions:
- PVB19 persistence in DCM can lead to myocardial ECM remodeling via MMPs and mitochondrial dysfunction.
- Biomarker analysis suggests potential for future apoptotic pathway activation rather than fibrosis.
- Antiviral therapy may be beneficial for PVB19-positive DCM patients by mitigating pathological myocardial remodeling.
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