Arthritis and rheumatism · 2007
Analysis of vascular gene expression in arthritic synovium by laser-mediated microdissection.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Hashimoto Atsushi, Tarner Ingo H, Bohle Rainer M, Gaumann Andreas, Manetti Mirko, Distler Oliver, Steinmeyer Jürgen, Ulfgren Ann-Kristin, Schulz Andreas, Gay Steffen, Müller-Ladner Ulf, Neumann Elena
Аннотация
OBJECTIVE: In rheumatoid arthritis (RA), formation of new blood vessels is necessary to meet the nutritional and oxygen requirements of actively proliferating synovial tissue. The aim of this study was to analyze the specific synovial vascular expression profiles of several angiogenesis-related genes as well as CD82 in RA compared with osteoarthritis (OA), using laser-mediated microdissection (LMM).
METHODS: LMM and subsequent real-time polymerase chain reaction were used in combination with immunohistochemical analysis for area-specific analysis of messenger RNA (mRNA) and protein expression of vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR-1), VEGFR-2, hypoxia-inducible factor 1alpha (HIF-1alpha), HIF-2alpha, platelet-derived growth factor receptor alpha (PDGFRalpha), PDGFRbeta, inhibitor of DNA binding/differentiation 2 (Id2), and CD82 in RA and OA synovial microvasculature and synovial lining.
RESULTS: Expression of Id2 mRNA was significantly lower in RA synovial vessels compared with OA synovial vessels (P=0.0011), whereas expression of VEGFR-1 was significantly higher in RA (P=0.0433). No differences were observed for the other parameters. At the protein level, no statistically significant differences were observed for any parameter, although Id2 levels were 2.5-fold lower in RA (P=0.0952). However, the number of synovial blood vessels and the number of VEGFR-2-expressing blood vessels were significantly higher in RA compared with OA.
CONCLUSION: Our results underscore the importance of area-specific gene expression analysis in studying the pathogenesis of RA and support LMM as a robust tool for this purpose. Of note, our results indicate that previously described differences between RA and OA in the expression of angiogenic molecules are attributable to higher total numbers of synovial and vascular cells expressing these molecules in RA rather than higher expression levels in the individual cells.
METHODS: LMM and subsequent real-time polymerase chain reaction were used in combination with immunohistochemical analysis for area-specific analysis of messenger RNA (mRNA) and protein expression of vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR-1), VEGFR-2, hypoxia-inducible factor 1alpha (HIF-1alpha), HIF-2alpha, platelet-derived growth factor receptor alpha (PDGFRalpha), PDGFRbeta, inhibitor of DNA binding/differentiation 2 (Id2), and CD82 in RA and OA synovial microvasculature and synovial lining.
RESULTS: Expression of Id2 mRNA was significantly lower in RA synovial vessels compared with OA synovial vessels (P=0.0011), whereas expression of VEGFR-1 was significantly higher in RA (P=0.0433). No differences were observed for the other parameters. At the protein level, no statistically significant differences were observed for any parameter, although Id2 levels were 2.5-fold lower in RA (P=0.0952). However, the number of synovial blood vessels and the number of VEGFR-2-expressing blood vessels were significantly higher in RA compared with OA.
CONCLUSION: Our results underscore the importance of area-specific gene expression analysis in studying the pathogenesis of RA and support LMM as a robust tool for this purpose. Of note, our results indicate that previously described differences between RA and OA in the expression of angiogenic molecules are attributable to higher total numbers of synovial and vascular cells expressing these molecules in RA rather than higher expression levels in the individual cells.
Предметные рубрики MeSH
AdultAgedAged, 80 and overArthritis, RheumatoidBasic Helix-Loop-Helix ProteinsFemaleGene ExpressionHumansHypoxia-Inducible Factor 1, alpha SubunitInhibitor of Differentiation Protein 2Kangai-1 ProteinMaleMicrodissectionMiddle AgedNeovascularization, PathologicOsteoarthritisRNA, MessengerReceptor, Platelet-Derived Growth Factor alphaReceptor, Platelet-Derived Growth Factor betaSynovial MembraneTranscription FactorsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2Endothelial PAS Domain-Containing Protein 1