NLRP1 deficiency significantly protected against aortic banding-induced cardiac hypertrophy, inflammation, and fibrosis in mice by reducing activation of MAPK, NF-κB, and TGF-β/Smad pathways.
Does NLRP1 deficiency protect against pressure overload-induced cardiac hypertrophy in preclinical models?
NLRP1 deficiency protects against pressure overload-induced cardiac hypertrophy by inhibiting MAPK, NF-κB, and TGF-β/Smad signaling pathways in preclinical models.
BACKGROUND/AIMS: Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a cytoplasmic protein, involved in autoimmune diseases, mammalian reproduction, neuronal cell death, and stroke. However, the role of NLRP1 in cardiac hypertrophy remains unclear. We used in vivo and in vitro models to investigate the effects of NLRP1 on cardiac hypertrophy. METHODS: We used NLRP1-deficient mice and cultured neonatal rat cardiomyocytes with gain and loss of NLRP1 function. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements, and by pathological and molecular analysis. RESULTS: Eight weeks after aortic banding (AB), NLRP1 deficiency significantly inhibited aortic banding-induced cardiac hypertrophy, inflammation, and fibrosis. Activation of MAPK, NF-κB, and TGF-β/Smad pathways was reduced in NLRP1-knockout (KO) mice compared with that in wild-type (WT) mice. Consistent with these results, in vitro studies, performed using cultured neonatal mouse cardiomyocytes, confirmed that NLRP1 deficiency protects against cardiomyocyte hypertrophy induced by isoproterenol (PE); this protective activity was associated with the arrest of MAPK and NF-κB signaling. CONCLUSIONS: Our data illustrates that NLRP1 plays a crucial role in the development of cardiac hypertrophy via positive regulation of the MAPK, NF-κB, and TGF-β/Smad signaling pathways.
Zong et al. (Mon,) conducted a other in Cardiac hypertrophy. NLRP1 deficiency vs. Wild-type (WT) mice was evaluated on Cardiac hypertrophy, inflammation, and fibrosis. NLRP1 deficiency significantly protected against aortic banding-induced cardiac hypertrophy, inflammation, and fibrosis in mice by reducing activation of MAPK, NF-κB, and TGF-β/Smad pathways.