Paavonen Karri, Mandelin Jami, Partanen Taina, Jussila Lotta, Li Tian-Fang, Ristimaki Ari, Alitalo Kari, Konttinen Yrjö T
Molecular/Cancer Biology Laboratory, Biomedicum Helsinki, University of Helsinki, Finland.
J Rheumatol. 2002 Jan;29(1):39-45.
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.
Immunohistochemical staining and messenger RNA analysis from control and arthritic synovial membrane specimens.
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.
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.
在滑膜标本中定位血管内皮生长因子C（VEGF-C）和VEGF-D，并研究它们与血管和淋巴管中的VEGFR-2和VEGFR-3受体的关系。
对对照和关节炎滑膜标本进行免疫组织化学染色和信使核糖核酸分析。
定量逆转录聚合酶链反应显示，在研究的类风湿关节炎（RA）、骨关节炎和对照患者组中，VEGF-C信使核糖核酸拷贝数高于VEGF-D信使核糖核酸拷贝数（p<0.01）。免疫组织化学染色将VEGF-C定位于滑膜衬里细胞层、周细胞和血管平滑肌细胞。与对照滑膜相比，强直性脊柱炎（AS）和RA滑膜衬里中VEGF-C阳性细胞数量增加。然而，与对照滑膜衬里不同，在AS或RA滑膜衬里中几乎未检测到VEGF-D。表达VEGFR-2的基质血管，对血管内皮标志物PAL-E和基底膜标志物层粘连蛋白也呈阳性，在RA和AS中比对照中更丰富。有趣的是，淋巴管内皮受体VEGFR-3也在大多数滑膜血管中表达，尤其是在衬里下毛细血管和小静脉中。
VEGF-C在关节炎关节的肥厚滑膜衬里中强烈表达，而VEGF-D在AS和RA中表达非常低。VEGF-C和VEGF-D在周细胞和平滑肌细胞中的表达表明这些因子可能在维持血管稳态中起作用。VEGF受体VEGFR-2和VEGFR-3存在于大多数衬里下血管中。衬里下血管中淋巴管标志物VEGFR-3的表达可能与液体过滤和/或窗孔有关。RA中相对较少的淋巴管以及血管通透性增加可能导致组织水肿和关节僵硬的发生。
