Tags

Type your tag names separated by a space and hit enter

Analysis of vascular gene expression in arthritic synovium by laser-mediated microdissection.
Arthritis Rheum. 2007 Apr; 56(4):1094-105.AR

Abstract

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.

Authors+Show Affiliations

Department of Medicine and Rheumatology, Justus-Liebig-University of Giessen, Giessen, and University Hospital Regensburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17393418

Citation

Hashimoto, Atsushi, et al. "Analysis of Vascular Gene Expression in Arthritic Synovium By Laser-mediated Microdissection." Arthritis and Rheumatism, vol. 56, no. 4, 2007, pp. 1094-105.
Hashimoto A, Tarner IH, Bohle RM, et al. Analysis of vascular gene expression in arthritic synovium by laser-mediated microdissection. Arthritis Rheum. 2007;56(4):1094-105.
Hashimoto, A., Tarner, I. H., Bohle, R. M., Gaumann, A., Manetti, M., Distler, O., Steinmeyer, J., Ulfgren, A. K., Schulz, A., Gay, S., Müller-Ladner, U., & Neumann, E. (2007). Analysis of vascular gene expression in arthritic synovium by laser-mediated microdissection. Arthritis and Rheumatism, 56(4), 1094-105.
Hashimoto A, et al. Analysis of Vascular Gene Expression in Arthritic Synovium By Laser-mediated Microdissection. Arthritis Rheum. 2007;56(4):1094-105. PubMed PMID: 17393418.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of vascular gene expression in arthritic synovium by laser-mediated microdissection. AU - Hashimoto,Atsushi, AU - Tarner,Ingo H, AU - Bohle,Rainer M, AU - Gaumann,Andreas, AU - Manetti,Mirko, AU - Distler,Oliver, AU - Steinmeyer,Jürgen, AU - Ulfgren,Ann-Kristin, AU - Schulz,Andreas, AU - Gay,Steffen, AU - Müller-Ladner,Ulf, AU - Neumann,Elena, PY - 2007/3/30/pubmed PY - 2007/5/11/medline PY - 2007/3/30/entrez SP - 1094 EP - 105 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 56 IS - 4 N2 - 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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/17393418/Analysis_of_vascular_gene_expression_in_arthritic_synovium_by_laser_mediated_microdissection_ L2 - https://doi.org/10.1002/art.22450 DB - PRIME DP - Unbound Medicine ER -