Role of inflammation in right ventricular damage and repair following experimental pulmonary embolism in rats
| Autor: | Watts, John Albert, Gellar, Michael Aaron, Obraztsova, Maria, Kline, Jeffrey Allen, Zagorski, John |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Genetic Markers
Male Time Factors Staining and Labeling Neutrophils Gene Expression Profiling Heart Ventricles Macrophages Myocardium Ventricular Dysfunction Right Original Articles Rats Rats Sprague-Dawley Neutrophil Infiltration Gelatinases Animals Regeneration Pulmonary Embolism Oligonucleotide Array Sequence Analysis |
| Popis: | Right ventricular (RV) dysfunction is associated with poor clinical outcome following pulmonary embolism (PE). Previous studies in our laboratory show that influx of neutrophils contributes to acute RV damage seen in an 18 h rat model of PE. The present study describes the further progression of inflammation over 6 weeks and compares the neutrophil and monocyte responses. The RV outflow tract became white in colour by day 1 with influx of neutrophils (tissue myeloperoxidase activity increased 17-fold) and mononuclear cells with characteristics of M1 phenotype (high in Ccl20, Cxcl10, CcR2, MHCII, DNA microarray analysis). Matrix metalloproteinase activities were increased and tissue was thinned to produce a translucent appearance in weeks 1 through 6 in 40% of hearts. RV contractile function was significantly reduced at 6 weeks of PE. In this later phase, there was accumulation of myofibroblasts, the presence of mononuclear cells with M2 characteristics (high in scavenger mannose receptors, macrophage galactose lectin 1, PDGFR1, PDGFRbeta), enrichment of the subendocardial region of the RV outflow tract with neovesels (alpha-smooth muscle immunohistochemistry) and deposition of collagen fibres (picrosirius red staining) beginning scar formation. Thus, while neutrophil response is associated with the early, acute inflammatory events, macrophage cells continue to be present during the proliferative phase and initial deposition of collagen in this model, changing from the M1 to the M2 phenotype. This suggests that the macrophage cell response is biphasic. |
| Databáze: | OpenAIRE |
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