(285) Heme-Binding Protein 1 Delivered via Pericyte-Derived Extracellular Vesicles Improves Neurovascular Regeneration in a Mouse Model of Cavernous Nerve Injury

Abstract

Abstract Introduction As a peripheral nerve injury disease, cavernous nerve injury (CNI) caused by prostate cancer surgery and other pelvic surgery causes organic damage to cavernous blood vessels and nerves, thereby significantly attenuating the response to phosphodiesterase-5 inhibitors. Objective Here, we investigated the role of heme-binding protein 1 (Hebp1) in erectile function using a mouse model of bilateral CNI, which is known to promote angiogenesis and improve erection in diabetic mice. Methods To investigate the efficacy and mechanism of Hebp1 in restoring erectile function in CNI-induced ED mice, we injected recombinant mouse Hebp1 protein into the penis of CNI-induced ED mice. Detailed mechanisms were assessed using Signaling Explorer Antibody Arrays on penile tissue from CNI-induced ED mice; MPG tissue and Schwann cells were cultured in the presence of 2.5 μg/ml LPS. Results We found a potent neurovascular regenerative effect of Hebp1 in CNI mice, demonstrating that exogenously delivered Hebp1 improved erectile function by promoting the survival of cavernous endothelial-mural cells and neurons. We further found that endogenous Hebp1 delivered by mouse cavernous pericyte (MCP)-derived extracellular vesicles promoted neurovascular regeneration in CNI mice. Moreover, Hebp1 achieved these effects by reducing vascular permeability through regulation of claudin family proteins. Conclusions Our findings provide new insights into Hebp1 as a neurovascular regeneration factor and demonstrate its potential therapeutic application to various peripheral nerve injuries. Disclosure No.