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Abstract

Vascular endothelial growth factors C and D and their VEGFR-2 and 3 receptors in blood and lymphatic vessels in healthy and arthritic synovium.

Karri Paavonen, Jami Mandelin, Taina Partanen, Lotta Jussila, Tian-Fang Li, Ari Ristimaki, Kari Alitalo and Yrjö T Konttinen
The Journal of Rheumatology January 2002, 29 (1) 39-45;
Karri Paavonen
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Jami Mandelin
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Taina Partanen
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Lotta Jussila
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Tian-Fang Li
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Ari Ristimaki
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Kari Alitalo
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Yrjö T Konttinen
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Abstract

OBJECTIVE: To localize vascular endothelial growth factor C (VEGF-C) and VEGF-D in synovial specimens in relation to their VEGFR-2 and VEGFR-3 receptors in blood and lymphatic vessels. METHODS: Immunohistochemical staining and messenger RNA analysis from control and arthritic synovial membrane specimens. RESULTS: Quantitative RT-PCR disclosed that VEGF-C mRNA copy numbers were higher than VEGF-D mRNA copy numbers in the rheumatoid arthritis (RA), osteoarthritis, and control patient groups studied (p < 0.01). Immunohistochemical staining localized VEGF-C to synovial lining cell layer, pericytes, and smooth muscle cells of blood vessels. The number of VEGF-C positive cells was increased in the synovial lining of ankylosing spondylitis (AS) and RA compared to control synovium. However, in contrast to control synovial lining, little if any VEGF-D was detected in AS or RA synovial lining. VEGFR-2 expressing stromal blood vessels, also positive for the vascular endothelial marker PAL-E and the basement membrane marker laminin, were more abundant in RA and AS than in controls. Interestingly, the lymphatic endothelial receptor VEGFR-3 was also expressed in most synovial vessels, especially in the sublining capillaries and venules. CONCLUSION: VEGF-C is strongly expressed in the hypertrophic synovial lining of arthritic joints, whereas VEGF-D expression is very low in AS and RA. The expression of VEGF-C and VEGF-D in pericytes and smooth muscle cells suggests that these factors may have a role in maintaining vascular homeostasis. The VEGF receptors VEGFR-2 and VEGFR-3 are present in most of the sublining blood vessels. The expression of the lymphatic marker VEGFR-3 in the sublining blood vessels may relate to fluid filtration and/or fenestrations. The relatively few lymphatic vessels along with increased vascular permeability in RA may contribute to the development of tissue edema and joint stiffness.

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The Journal of Rheumatology
Vol. 29, Issue 1
1 Jan 2002
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Vascular endothelial growth factors C and D and their VEGFR-2 and 3 receptors in blood and lymphatic vessels in healthy and arthritic synovium.
Karri Paavonen, Jami Mandelin, Taina Partanen, Lotta Jussila, Tian-Fang Li, Ari Ristimaki, Kari Alitalo, Yrjö T Konttinen
The Journal of Rheumatology Jan 2002, 29 (1) 39-45;

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Vascular endothelial growth factors C and D and their VEGFR-2 and 3 receptors in blood and lymphatic vessels in healthy and arthritic synovium.
Karri Paavonen, Jami Mandelin, Taina Partanen, Lotta Jussila, Tian-Fang Li, Ari Ristimaki, Kari Alitalo, Yrjö T Konttinen
The Journal of Rheumatology Jan 2002, 29 (1) 39-45;
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