Work

Inhibition of inducible nitric oxide synthase (iNOS) alleviates thoracic aortic aneurysm by regulating mitochondrial dynamics

Year: 2025

Type: article

Abstract: Thoracic aortic aneurysm (TAA) is life-threatening once developing to dissection (TAAD) or rupture and currently there is no effective pharmacological treatment. The abnormal activity of inducible nitric oxide synthase (iNOS) has been related with syndromic TAA, but its potential role in non-syndromic TAA is unknown. Here we identified elevations of inducible nitric oxide synthase (iNOS) and its downstream protein kinase G1 (PRKG1) in both human non-syndromic TAA and β-aminopropionitrile (BAPN)-induced mouse model of TAA. The iNOS-specific inhibitor 1400W effectively inhibited the formation of BAPN-induced TAA and TAAD in mice, improved aortic extracellular matrix (ECM) degradation, and reduced TAAD-associated death. The protective effect of 1400W on TAA was likely achieved by decreasing mitochondrial fusion and increasing mitochondrial fission, along with reduced reactive oxygen species (ROS) production and increased NAD + /NADH level, in human aortic vascular smooth muscle cells (HASMCs). In conclusion, here we confirm the protective effect of 1400W on non-syndromic TAA and suggest the value of regulating the iNOS-PRKG1-mitochondrial dynamics signaling in the treatment of non-syndromic TAA.

Source: European Journal of Pharmacology

DOI: 10.1016/j.ejphar.2025.178071