Mechanism of Galectin-3 in arteriogenic erectile dysfunction via TLR4/MyD88/NF-κB pathway

Abstract

Abstract Galectin-3 (Gal-3), a multifunctional protein, has been linked to fibrosis and inflammation in the cardiovascular system. This study endeavors to examine the impact of Gal-3 on inflammation and fibrosis in arteriogenic erectile dysfunction (A-ED) and the underlying mechanisms. To induce arterial injury, we utilized cuffs on the periaqueductal common iliac arteries of Sprague-Dawley (SD) rats and administered a high-fat diet to co-induce local atherosclerosis. Our results show that we have successfully developed a novel A-ED model that was validated based on histological evidence. In vivo, the vascular lumen of rats subjected to a high-fat diet and cuff placement exhibited significant narrowing, accompanied by upregulation of Gal-3, TLR4, and MyD88 expression in the penile cavernosal. This led to the activation of NF-κB-p65, resulting in reduced intracavernosal pressure, endothelial nitric oxide synthase expression, and smooth muscle content, promoting inflammation and fibrosis. However, treatment with Gal-3 inhibitor-modified citrus pectin (MCP) significantly improved these phenomena. In Vitro, knocking down Gal-3 led to a significant reduction in TLR4, MyD88, and NF-κB-p65 expression in CCSMCs, decreasing inflammation levels. In conclusion, inhibiting Gal-3 may improve A-ED by reducing inflammation, endothelial injury, and fibrosis in the penile corpus cavernosum through the TLR4/MyD88/NF-κB pathway. The findings highlight the potential therapeutic target of Gal-3 in A-ED.