The etiology of IC/BPS is multifactorial; thus, pathophysiology-based phenotyping is needed for tailored treatments of IC/BPS patients. In this regard, it is now generally agreed that, when focusing on inflammatory responses in the bladder mucosa, IC/BPS is divided into two major phenotypes. One is "interstitial cystitis (IC)," which is a chronic inflammatory disorder with Hunner lesions, and the other is "bladder pain syndrome (BPS)," in which inflammatory changes are minimal without Hunner lesions. However, as another important pathophysiological change in the IC/BPS bladder, angiogenetic responses including overexpression of angiogenic growth factors, such as platelet-derived endothelial cell growth factor (PD-ECGF), vascular endothelial growth factor (VEGF), and CD31 (platelet endothelial cell adhesion molecule; PECAM-1), have been shown to correlate with symptom severity in Hunner-type IC and non-Hunner IC/BPS patients. In addition, previous studies in IC/BPS patients showed that glomerulations or mucosal bleeding during hydrodistension occur due to the rupture of bladder mucosal capillary vessels in association with PD-ECGF and VEGF overexpression. Furthermore, upregulation of angiogenic factors and their signaling pathways has been detected in animal models of IC/BPS induced by bladder inflammation or psychological stress. Thus, angiogenic factor overexpression and immature microvessel formation in the bladder mucosa could be another important diagnostic criterion in addition to the inflammatory status for further phenotyping of IC/BPS.
International journal of urology : official journal of the Japanese Urological Association. 2026 May [Epub]
Naoki Yoshimura, Akira Furuta, Yuki Tobisawa, Taro Igarashi, Tetsuichi Saito, Tomohiro Ueda
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Department of Urology, Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan., Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan., Department of Urology, Ueda Clinic, Kyoto, Japan.