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Sex-Specific Effects of the Nlrp3 Inflammasome on Atherogenesis in LDL Receptor-Deficient Mice.


ABSTRACT: In the Ldlr -/- mouse model of atherosclerosis, female Nlrp3 -/- bone marrow chimera and Nlrp3 -/- mice developed significantly smaller lesions in the aortic sinus and decreased lipid content in aorta en face, but a similar protection was not observed in males. Ovariectomized female mice lost protection from atherosclerosis in the setting of NLRP3 deficiency, whereas atherosclerosis showed a greater dependency on NLRP3 in castrated males. Thus, castration increased the dependency of atherosclerosis on the NLRP3 inflammasome, suggesting that testosterone may block inflammation in atherogenesis. Conversely, ovariectomy reduced the dependency on NLRP3 inflammasome components for atherogenesis, suggesting that estrogen may promote inflammasome-mediated atherosclerosis.

SUBMITTER: Chen S 

PROVIDER: S-EPMC7315187 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Sex-Specific Effects of the Nlrp3 Inflammasome on Atherogenesis in LDL Receptor-Deficient Mice.

Chen Shuang S   Markman Janet L JL   Shimada Kenichi K   Crother Timothy R TR   Lane Malcolm M   Abolhesn Amanda A   Shah Prediman K PK   Arditi Moshe M  

JACC. Basic to translational science 20200520 6


In the <i>Ldlr</i> <sup><i>-/-</i></sup> mouse model of atherosclerosis, female <i>Nlrp3</i> <sup><i>-/-</i></sup> bone marrow chimera and <i>Nlrp3</i> <sup><i>-/-</i></sup> mice developed significantly smaller lesions in the aortic sinus and decreased lipid content in aorta en face, but a similar protection was not observed in males. Ovariectomized female mice lost protection from atherosclerosis in the setting of NLRP3 deficiency, whereas atherosclerosis showed a greater dependency on NLRP3 in  ...[more]

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