Infection of Cardiomyocytes and Induction of Left Ventricle Dysfunction by Neurovirulent Polytropic Murine Retrovirus

Abstract

Viral infections of the heart are a causative factor of myocarditis as well as of sudden, unexpected deaths of children, yet the mechanisms of pathogenesis remain unclear, in part due to the relatively few animal models of virus-induced myocarditis. In the current study, we examined the ability of polytropic murine retroviruses to infect the heart and induce cardiac dysfunction. In situ hybridization and immunohistochemistry analysis detected virus-infected cardiomyocytes and macrophages in the heart. A significant decrease in left ventricle function, as measured by fractional shortening, was detected in mice infected with the neurovirulent retrovirus Fr98 but not in mice infected with the nonneurovirulent retrovirus Fr54. Virus infection was not associated with consistent findings of fibrosis or substantial cellular infiltrate. Fr98-induced left ventricle dysfunction was associated with a higher virus load, increased mRNA expression of the macrophage marker F4/80, increased chemokine production, and a small number of apoptotic cells in the heart.

Tesaglitazar, a Dual Peroxisome Proliferator- Activated Receptor Agonist (PPARα/γ), Improves Metabolic Abnormalities and Reduces Renal Injury in Obese Zucker Rats

“…As a result, PPARα increases insulin-stimulated glucose disposal in skeletal muscle, ameliorates IR and decreases fat load in adipose tissue in rodents [11,12,13,14,15,16,17,18,19,20,21,22,23]. Another complementary mechanism of combined activation of PPARα and γ when improving IR involves the induction of adipose tissue adiponectin receptors by PPARα and adiponectin by PPARγ, resulting in decreased infiltration of macrophages in adipose tissue, thereby ameliorating tissue inflammation and improving obesity-induced IR [24].…”

“…The desmin expression by immunofluorescence study was done with a protocol described by Khaleduzzaman et al [19]. For the detection of podocyte damage, slides were rehydrated and incubated overnight at 4°C with a 1:100 dilution of monoclonal mouse anti-human clone D33 isotype: IgG1ĸ (Dako, Carpinteria, Calif., USA).…”

Toll-Like Receptor 2 Recognition of the MicrosporidiaEncephalitozoonspp. Induces Nuclear Translocation of NF-κB and Subsequent Inflammatory Responses

“…The amplification of TNF-␣, TLR2, and TLR4 cDNA was completed using validated primers and the RT 2 Sybr green-fluorescein master mix. All data were normalized to the ␤-actin housekeeping gene, and gene expression was calculated as previously described (21). Briefly, the cycle threshold (C T ) value (log 2 ) for ␤-actin minus the C T value of the gene of interest for each sample (⌬C T ϭ C T of ␤-actin Ϫ C T of gene of interest) was calculated and is presented as the percentage of ␤-actin.…”

Analysis of Protein Levels of 24 Cytokines in Scrapie Agent-Infected Brain and Glial Cell Cultures from Mice Differing in Prion Protein Expression Levels

“…This method has been used previously to study expression of cytokines and other proteins in brain tissue homogenates (11,24,26). Therefore, in the present study, we used this method to analyze cytokine levels from scrapie agent-infected brain samples and correlated these findings with those from scrapie agent-stimulated primary astroglial and microglial cell cultures.…”