Fatty acid synthase inhibition improves hypertension-induced erectile dysfunction by suppressing oxidative stress and NLRP3 inflammasome-dependent pyroptosis through activating the Nrf2/HO-1 pathway DOI Creative Commons

Jiaochen Luan,

Mengchi Yu,

Qi Gu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Background Erectile dysfunction (ED) is a prevalent male sexual disorder, commonly associated with hypertension, though the underlying mechanisms remain poorly understood. Objective This study aims to explore role of Fatty acid synthase (Fasn) in hypertension-induced ED and evaluate therapeutic potential Fasn inhibitor C75. Materials methods function was assessed by determining intracavernous pressure/mean arterial pressure (ICP/MAP) ratio, followed collection cavernous tissue for transcriptomic non-targeted metabolomic analyses. In vitro , concentration 10 -6 M angiotensin II (Ang II) applied rat aortic endothelial cells (RAOECs) establish model hypertension. vivo spontaneously hypertensive rats (SHR) were randomly divided into two groups. The SHR+C75 group received intraperitoneal injections C75 at dose 2 mg/kg once week. After five weeks treatment, erectile assessed, penile tissues harvested further analysis. Molecular protein expression using Western blotting, qRT-PCR, immunofluorescence staining, immunohistochemistry. Results SHR exhibited ED, indicated reduced maximum ICP/MAP ratios. Histologically, corpus cavernosum showed elevated fibrosis dysfunction. Additionally, increased NLRP3 inflammasome, Caspase-1, GSDMD, pro-inflammatory cytokines IL-1β IL-18 observed. Multi-omics analysis revealed significant enrichment lipid metabolic pathways, identified as hub gene. siFasn enhanced antioxidant markers Nrf2 HO-1, ROS accumulation, suppressed GSDMD levels. treatment restored reversed dysfunction, accompanied decreased oxidative stress pyroptosis cavernosum. Conclusion These findings suggest that inhibition may offer promising strategy alleviating suppressing inflammasome-dependent cell via activation Nrf2/HO-1 pathway.

Language: Английский

Fatty acid synthase inhibition improves hypertension-induced erectile dysfunction by suppressing oxidative stress and NLRP3 inflammasome-dependent pyroptosis through activating the Nrf2/HO-1 pathway DOI Creative Commons

Jiaochen Luan,

Mengchi Yu,

Qi Gu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Background Erectile dysfunction (ED) is a prevalent male sexual disorder, commonly associated with hypertension, though the underlying mechanisms remain poorly understood. Objective This study aims to explore role of Fatty acid synthase (Fasn) in hypertension-induced ED and evaluate therapeutic potential Fasn inhibitor C75. Materials methods function was assessed by determining intracavernous pressure/mean arterial pressure (ICP/MAP) ratio, followed collection cavernous tissue for transcriptomic non-targeted metabolomic analyses. In vitro , concentration 10 -6 M angiotensin II (Ang II) applied rat aortic endothelial cells (RAOECs) establish model hypertension. vivo spontaneously hypertensive rats (SHR) were randomly divided into two groups. The SHR+C75 group received intraperitoneal injections C75 at dose 2 mg/kg once week. After five weeks treatment, erectile assessed, penile tissues harvested further analysis. Molecular protein expression using Western blotting, qRT-PCR, immunofluorescence staining, immunohistochemistry. Results SHR exhibited ED, indicated reduced maximum ICP/MAP ratios. Histologically, corpus cavernosum showed elevated fibrosis dysfunction. Additionally, increased NLRP3 inflammasome, Caspase-1, GSDMD, pro-inflammatory cytokines IL-1β IL-18 observed. Multi-omics analysis revealed significant enrichment lipid metabolic pathways, identified as hub gene. siFasn enhanced antioxidant markers Nrf2 HO-1, ROS accumulation, suppressed GSDMD levels. treatment restored reversed dysfunction, accompanied decreased oxidative stress pyroptosis cavernosum. Conclusion These findings suggest that inhibition may offer promising strategy alleviating suppressing inflammasome-dependent cell via activation Nrf2/HO-1 pathway.

Language: Английский

Citations

1