NLRP3 inflammasomes contribute to hyperhomocysteinemia-induced inflammation and atherosclerosis
- Author:
Renqing WANG
;
Nana MU
;
Xiaoying LOU
;
Yiqin WANG
;
Hongmei TAN
- Publication Type:Journal Article
- From:
Chinese Journal of Pathophysiology
2016;32(8):1492-1493
- CountryChina
- Language:Chinese
-
Abstract:
AIM:NLRP3 inflammasome was identified as the cellular machinery responsible for activation of inflammatory processes .The present study investigated whether the activation of NLRP 3 inflammasomes contributes to hyperhomocysteinemia ( HHcy)-induced in-flammation and atherosclerosis .METHODS:ApoE-/-mice were fed regular diet , high fat ( HF) diet or HF plus high methionine (HM) diet for 10 weeks.NLRP3 shRNA or scramble shRNA viral suspension was injected twice at the 2nd and the 6th weeks after HFHM treatment.The whole aortas and aortic root sections were stained with Oil Red O for atherosclerotic lesion .Plasma lipids, ho-mocysteine ( Hcy) , IL-1βand IL-18 levels were measured .We also examined the effect of Hcy on NLRP 3 inflammasomes activation in THP-1 differentiated macrophages in the presence or absence of NLRP 3 siRNA, caspase-1 inhibitor Z-WEHD-FMK, or antioxidant N-acetyl-L-cysteine ( NAC) .RESULTS:HFHM treatment induced HHcy in ApoE-/-mice.Increased plasma levels of IL-1βand IL-18, aggravated macrophage infiltration into atherosclerotic lesion , and accelerated development of atherosclerosis were detected in HHcy mice, which were associated with the activation of NLRP 3 inflammasomes.Silencing the NLRP3 gene significantly suppressed NLRP3 inflammasomes activation , reduced plasma levels of proinflammatory cytokines , attenuated macrophage infiltration , and improved HHcy-induced atherosclerosis .Moreover, we found that Hcy activated NLRP3 inflammasomes and promoted subsequent production of IL-1βand IL-18 in macrophages, which were blocked by NLRP3 gene silencing, Z-WEHD-FMK, or NAC.CONCLUSION:These data suggest that the activation of NLRP 3 inflammasomes contributes to HHcy-induced inflammation and atherosclerosis .Hcy activates NLRP3 inflammasomes in reactive oxygen species dependent pathway in macrophages .
