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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-1\u03b2, and IL-1\u03b2 was quantified by Western blotting; Nlrp1a, Nlrp3, Nlrc4, Pycard (Asc), Casp1, and Il1b gene expression was assessed by qPCR; and statistical analysis used Student\u2019s t test and ANOVA. Rats with infarction size &gt; 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.<\/jats:p>","DOI":"10.3390\/ijms27094140","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T09:03:37Z","timestamp":1778144617000},"page":"4140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Early Treatment with Lipid Core Nanoparticles-Associated Methotrexate on Cardiac Remodeling and Soleus Muscle Inflammasomes in Infarcted Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8219-6622","authenticated-orcid":false,"given":"Anna Clara C.","family":"Santos","sequence":"first","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3115-0795","authenticated-orcid":false,"given":"Mariana","family":"Gatto","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8103-3338","authenticated-orcid":false,"given":"Gustavo A. F.","family":"Mota","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7472-8019","authenticated-orcid":false,"given":"Patr\u00edcia A.","family":"Borim","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael C. F.","family":"Silva","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Luisa B.","family":"Meirelles","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9726-3901","authenticated-orcid":false,"given":"Lidiane M.","family":"Souza","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5824-5199","authenticated-orcid":false,"given":"Elida P. B.","family":"Ojopi","sequence":"additional","affiliation":[{"name":"Clinic Hospital, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eder A.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana U.","family":"Pagan","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula S.","family":"Marreiros","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-5068","authenticated-orcid":false,"given":"Gabriela","family":"Brandao","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Botucatu Medical School, Sao Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo A. 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