Increased vascular endothelial growth factor expression in patients with bladder pain syndrome/interstitial cystitis: its association with pain severity and glomerulations

OBJECTIVE To 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 METHODS Angiogenesis 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. RESULTS VEGF 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. CONCLUSIONS There 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.