Role of inflammation in right ventricular damage and repair following experimental pulmonary embolism in rats.
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.
Watts
John Albert
JA
Emergency Medicine Research, Carolinas Medical Center, Charlotte, NC 28203, USA. jwatts@carolinas.org
Gellar
Michael Aaron
MA
Obraztsova
Maria
M
Kline
Jeffrey Allen
JA
Zagorski
John
J
D000818:Animals; D018093:Gelatinases / Q000032:analysis; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006352:Heart Ventricles; D008264:Macrophages / Q000276:immunology; D008297:Male; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D011655:Pulmonary Embolism / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000276:immunology*; D013194:Staining and Labeling; D013997:Time Factors; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology
D005819:Genetic Markers; D018093:Gelatinases