Increased vascular endothelial growth factor expression in patients with bladder pain syndrome/interstitial cystitis: its association with pain severity and glomerulations
Increased vascular endothelial growth factor expression in patients with bladder pain syndrome/interstitial cystitis: its association with pain severity and glomerulations
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DOI：
10.1111/j.1464-410x.2009.08467.x
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发表时间：
2009-09-01
影响因子：
4.5
通讯作者：
Okuyama, Akihiko
中科院分区：
文献类型：
--
作者：
Kiuchi, Hiroshi;Tsujimura, Akira;Okuyama, Akihiko
目的确定膀胱疼痛综合征（BPS）/间质性膀胱炎（IC）患者膀胱中的血管生成特征，并评估这些特征与相关临床特征（包括盆腔疼痛和肾小球）之间的关系。高水平的血管内皮生长因子（VEGF）已被证明会诱导不成熟的血管生成，其中微血管周细胞覆盖不足，导致血管出血。对30例BPS/IC和肾小球患者以及10例对照患者的活检标本进行了免疫组化检测VEGF表达、微血管密度（MVD）和未成熟微血管。标本中微血管的周细胞覆盖被用作成熟微血管的指标，并通过CD 34和α-平滑肌肌动蛋白的双重免疫组织化学鉴定周细胞。微血管周细胞覆盖指数（MPI）计算为成熟血管与总血管的比率。BPS/IC组固有层血管内皮生长因子（VEGF）表达明显高于对照组（50% vs 10%，P < 0.05）。在BPS/IC患者中，重度疼痛组VEGF阳性表达率明显高于轻度疼痛组（78% vs38%，P < 0.05）。BPS/IC患者的MPI显著低于对照组（23%vs35%，P < 0.05），而MVD在BPS/IC和对照组之间无显著性差异。总之，VEGF可能有助于疼痛和促进BPS/IC中未成熟血管的形成，并且未成熟血管形成的增加可能在BPS/IC患者的肾小球中起作用。
OBJECTIVETo determine the angiogenic profiles in the bladder of patients with bladder pain syndrome (BPS)/interstitial cystitis (IC), and to evaluate the relationship between these profiles and associated clinical features including pelvic pain and glomerulations.PATIENTS AND METHODSAngiogenesis and angiogenic components are important in chronic inflammatory disease. High levels of vascular endothelial growth factor (VEGF) have been shown to induce immature angiogenesis, where microvessels have insufficient coverage of pericytes, resulting in haemorrhagic vessels. Biopsy specimens from 30 patients with BPS/IC and glomerulations, and 10 control patients, were examined immunohistochemically for VEGF expression, microvessel density (MVD) and immature microvessels. Pericyte coverage of microvessels in the specimens was used as an indicator of mature microvessels, and pericytes were identified by double-immunohistochemistry for CD34 and alpha-smooth muscle actin. The microvessel pericyte coverage index (MPI) was calculated as the ratio of mature vessels to total vessels. We also assessed the relationship between these angiogenic profiles and associated clinical features including pain and glomerulations.RESULTSVEGF expression in the lamina propria was significantly higher in BPS/IC than in control samples (50% vs 10%, P < 0.05). Among patients with BPS/IC, VEGF expression was significantly higher in those with severe pain than in those with mild pain (78% vs 38%, P < 0.05). The MPI was significantly lower in BPS/IC than in control samples (23% vs 35%, P < 0.05), whereas MVD did not differ significantly between BPS/IC and control samples.CONCLUSIONSThere is increased VEGF and immature vascularization in patients with BPS/IC, and VEGF expression is associated with the degree of pain described by patients. Taken together, VEGF might contribute to pain and promote the formation of immature vessels in BPS/IC, and the increased immature vascularization might have a role in glomerulations in patients with BPS/IC.