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

Abstract

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 α‐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.

Evaluation of oxidative stress status and antioxidant capacity in patients with painful bladder syndrome/interstitial cystitis: preliminary results of a randomised study

“…The severity of neuronal and myogenic damage is established considering the degree of oxidative stress, revealing the symptomatology of the disease. Although it is not yet clear whether it is a cause or a result, it is obvious that there are some microvascular changes causing oxidative stress in BPS/IC and that mature vessel elements [29], and therefore, blood flow to the bladder decrease in these patients. It has been shown in previous studies that BPS/IC coexists and resembles allergic diseases such as bronchial asthma and allergic rhinitis where mast cell activation and histamine secretion are seen [30,31].…”

Risk factors that affect the treatment of interstitial cystitis using intravesical therapy with a dimethyl sulfoxide cocktail

“…To date, the pathogenesis of cystoscopic glomerulations is not yet fully understood. Tamaki et al [21] and Kiuchi et al [22] found cystoscopic glomerulations to be highly associated with the overexpression of angiogenic growth factors in the bladder. In addition, Kiuchi et al [22] found that the expression of angiogenic growth factor is associated with the degree of pain described by IC patients.…”

“…Tamaki et al [21] and Kiuchi et al [22] found cystoscopic glomerulations to be highly associated with the overexpression of angiogenic growth factors in the bladder. In addition, Kiuchi et al [22] found that the expression of angiogenic growth factor is associated with the degree of pain described by IC patients. Thus, it seems likely that neovascularization promoted by angiogenic growth factors has an important role in the pathogenesis of glomerulations and IC.…”

Neuropilin-VEGF signaling pathway acts as a key modulator of vascular, lymphatic, and inflammatory cell responses of the bladder to intravesical BCG treatment

“…However, a working hypothesis is that regardless of the cause of urothelial injury, i.e., BCG, bacterial infection, or any noxious substance in the urine, the urinary bladder responds by increasing the production of VEGF that acts initially as a survival factor (16) but also has the capacity of increasing vascular permeability (24), leading to glomerulations (34,69), edema, and inflammation. The present findings add to existing evidence indicating that, in the urinary bladder, NRPs are expressed in the urothelium, immune cells, nerves, blood vessels, and lymphatic vessels and mediate the accumulation of VEGF tracer.…”