Role of NLRP3/Caspase-1/IL-1β inflammasome pathway in formation of aortic dissection in mice

Abstract

Objective To investigate the role and mechanism of NLRP3/Caspase-1/IL-1β inflammasome pathway in the formation of aortic dissection in mice. Methods Fifty male C57BL/6 mice (3 weeks old, body weight 10~13 g) were divided into control group (n=10, normal diet), β-aminopropionitrile (BAPN) group [n=20, drink water containing 1 g/(kg·d) BAPN], and BAPN+ MCC950 group [n=20, drink water containing 1 g/(kg·d) BAPN and intraperitoneal injection of 20 mg/(kg·d) NLRP3 inhibitor, MCC950] by random sampling. Water intake, body weight, incidence of aortic dissection and aortic dissection-related mortality were recorded. The inflammatory infiltration in the aorta was observed with HE staining, elastic fiber breakage was observed by elastic Van Gieson (EVG) staining, average fluorescence intensity of NLRP3, IL-1β, α-SMA and OPN was detected by immunofluorescence assay, and protein expression levels of NLRP3, Caspase-1, ASC, IL-1β, α-SMA and OPN were measured with Western blotting. Results No aortic dissection or death was observed in the control group. The BAPN group had an incidence of aortic dissection of 80%, aortic dissection-related mortality of 35%, and obvious broken elastic fibers and inflammatory infiltrate in the aortic wall, and increased expression levels of NLRP3, Caspase-1, ASC and IL-1β, decreased contractile α-SMA and increased synthetic protein OPN when compared with the control group (P < 0.05). While MCC950 treatment decreased the incidence of aortic dissection (80% vs 35%, P=0.004) and aortic dissection-related mortality (35% vs 15%, P=0.144), alleviated the broken elastic fibers and inflammatory infiltrate in the aortic wall, and down-regulated the expression of NLRP3, Caspase-1, ASC and IL-1β, enhanced contractile α-SMA and decreased the synthetic protein when compared with the BAPN group (P < 0.05). Conclusion The occurrence of aortic dissection in mice is associated with activation of NLRP3/Caspase-1/IL-1β inflammasome pathway. NLRP3 inhibitor, MCC950, can reduce the occurrence of aortic dissection and show a protective effect on blood vessels.

Keywords

• aortic dissection
• aortic aneurysm
• nlrp3
• signaling pathway