Work

Modified vacuum erection device therapy attenuates smooth muscle phenotypic remodeling via the HIF-1α/CYCS/mitochondrial axis to improve erectile function in rats with bilateral cavernous nerve injury

Year: 2026

Type: article

Abstract: Erectile dysfunction (ED), caused by bilateral cavernous nerve injury (BCNI), is a common complication after radical prostatectomy. Vacuum erection device (VED) therapy has been employed for the rehabilitation of this type of ED by ameliorating cavernous ischemia and hypoxia, and hypoxia-inducible factor-1α (HIF-1α) serves as a critical molecule mediating cellular adaptation to hypoxic environments. However, the optimal timing of VED initiation remains incompletely defined, and the molecular mechanisms linking hypoxia to corpus cavernosum smooth muscle cells (CCSMCs) phenotypic remodeling remain unclear. Through in vivo and in vitro experiments, such as the construction of a BCNI rat model, erectile function assessment, establishment of a primary CCSMC hypoxia model, phenotypic detection, and CUT&Tag-qPCR, we investigated the effects and mechanisms of modified VED (with an advanced therapeutic window, while vacuum parameters and frequency were identical to conventional VED) on erectile function in BCNI rats. In vivo experiments confirmed that modified VED exhibited superior efficacy compared with conventional therapy, attenuating phenotypic remodeling of cavernous smooth muscle and improving erectile function in BCNI rats. In vitro experiments demonstrated that HIF-1α plays a pivotal role in hypoxia-induced phenotypic remodeling of CCSMCs, with its overexpression exacerbating and its knockdown attenuating this process. Mechanistically, HIF-1α directly transcriptionally activates cytochrome c, somatic (CYCS). Knockdown of CYCS or targeted mitochondrial antioxidant intervention restored mitochondrial function and attenuated phenotypic remodeling of CCSMCs. Modified VED improves erectile function in BCNI rats by inhibiting the HIF-1α/CYCS axis, alleviating mitochondrial dysfunction, and attenuating phenotypic remodeling of CCSMCs. These findings provide a preclinical mechanistic basis for further investigation of earlier VED intervention in BCNI-associated ED.

Source: Cell Biology and Toxicology

DOI: 10.1007/s10565-026-10288-8