Background
Vascular remodeling and inflammation are involved in aortic aneurysm (AA) and aortic dissection (AD). TGF-β1 signaling is involved in tissue fibrosis, extracellular matrix remodeling and inflammation, which are linked with AA and AD. The inhibition of NLRP3 inflammasome suppresses AA and AD. Hydrogen sulfide (H2S) exerts anti-vascular remodeling and anti-inflammatory properties, but little is known about its action on AA and AD progression.
Conclusions
These data support a crosstalk between TGF-β1 signaling and NLRP3 inflammasome. H2S inhibits AA and AD progression via blocking the crosstalk.
Methods
The effect of H2S on AA and AD formation was investigated in Sprague-Dawley (SD) rat fed a normal diet supplemented with 0.25% β-aminopropionitrile (BAPN). HE staining, Masson's trichrome staining, Picrosirius red staining and EVG staining were to evaluate vascular remodeling in the aortic wall. Western blotting and IHC were to detect the expression of TGF-β1 and matrix metalloproteinases (MMPs) and NLRP3 inflammasome-associated proteins. The interaction between TGF-β1 signaling and NLRP3 inflammasome was explored in Human aortic vascular smooth muscle cells (HA-VSMCs).
Results
H2S alleviated AA and AD progression. Specifically, it improved irregular tissue arrangement and vascular fibrosis, increased the expression of elastin fibers, decreased collagen deposition and the expression of TGF-β1 and matrix metalloproteinases (MMP-2/9). In addition, H2S inhibited the expression of proteins involved in NLRP3 inflammasome. Furthermore, H2S down-regulated TGF-β1 signaling and then ameliorated vascular fibrosis by preventing NLRP3 inflammasome activation. Finally, H2S inhibited NLRP3 inflammasome activation and decreased the level of IL-1β by disrupting TGF-β1 signaling. Conclusions: These data support a crosstalk between TGF-β1 signaling and NLRP3 inflammasome. H2S inhibits AA and AD progression via blocking the crosstalk.