Early MTX-LDE administration reduced NLRP1 and NLRC4 protein expression in soleus muscle without improving cardiac remodeling in rats with myocardial infarction.
Does early MTX-LDE administration improve cardiac remodeling and reduce soleus muscle inflammasomes in infarcted rats?
Early administration of lipid core nanoparticle-associated methotrexate reduces skeletal muscle inflammasome expression but worsens diastolic function in a rat model of myocardial infarction.
Substances released by cardiomyocytes after myocardial infarction (MI) lead to inflammasome assembly. Heart failure (HF) is associated with skeletal muscle inflammation. Methotrexate (MTX) reduces cardiovascular outcomes in chronic inflammation patients. Lipid core nanoparticle-associated MTX (MTX-LDE) attenuated cardiac remodeling in MI rats. We investigated the effects of early MTX-LDE administration on cardiac remodeling and inflammasomes in soleus muscle of MI rats. Wistar rats were separated into Sham, MI, and MI-MTX groups. MTX was initiated 24 h after MI at 1 mg/kg/week intraperitoneally for 10 weeks. Soleus protein expression of NLRP1, NLRP3, NLRC4, ASC, procaspase-1, Caspase-1, pro-IL-1β, and IL-1β was quantified by Western blotting; Nlrp1a, Nlrp3, Nlrc4, Pycard (Asc), Casp1, and Il1b gene expression was assessed by qPCR; and statistical analysis used Student’s t test and ANOVA. Rats with infarction size > 35% total left ventricle (LV) area were included in the study; infarction size did not differ between groups. Echocardiogram showed infarcted groups with LV dilation and dysfunction. Diastolic function was worse in MI-MTX than MI. NLRP1 and NLRC4 protein expression was lower in MI-MTX than Sham. Expression of other proteins and gene expression did not differ between groups. Early MTX-LDE administration reduces NLRP1 and NLRC4 protein expression in soleus muscle without improving cardiac remodeling in rats.
Santos et al. (Wed,) conducted a other in Myocardial infarction. Lipid core nanoparticle-associated MTX (MTX-LDE) vs. Sham and MI groups was evaluated on Cardiac remodeling and inflammasomes in soleus muscle. Early MTX-LDE administration reduced NLRP1 and NLRC4 protein expression in soleus muscle without improving cardiac remodeling in rats with myocardial infarction.