{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:26:49Z","timestamp":1787005609885,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize protein expression of NLRP3 inflammasome pathway components (NLRP3, TXNIP, ASC, IL-1\u03b2, IL-18, Caspase-1) in failing myocardium alongside exploratory mRNA profiling, elucidate their correlation with gut microbiota 16S rRNA gene profiles and the metabolite trimethylamine N-oxide (TMAO), and evaluate how dietary protein restriction and probiotic intervention modulate these pathways to influence heart failure progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Five groups of male SD rats were established: Control, HF, HF + Pro, LHF, and LHF + Pro, using abdominal aortic constriction. Comprehensive genomic and molecular analyses included: (1) quantitative real-time PCR (qRT-PCR) profiling of six key inflammasome genes (NLRP3, TXNIP, ASC, IL-1\u03b2, IL-18, Caspase-1); (2) Western blot protein quantification of the NLRP3 pathway; (3) gut microbiota 16S rRNA gene sequencing (V3-V4 region, Illumina NovaSeq); (4) serum biomarker enzyme-linked immunosorbent assay (IL-18, IL-1\u03b2, TNF-\u03b1, brain natriuretic peptide, TMAO); and (5) histopathological and ultrastructural analysis of myocardial tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum IL-18 protein levels were significantly elevated in the LHF group compared to controls (P &amp;lt; 0.05) by ELISA, with the most pronounced increase observed under dietary protein restriction; however, IL-18 mRNA expression by qRT-PCR showed directionally consistent but statistically non-significant trends across groups (P = 0.929, n = 3 per group). TMAO levels were decreased in HF and HF + Pro groups but paradoxically elevated in the LHF group, a finding discussed in detail in the context of dietary substrate availability and hepatic FMO3 activity. Western blot results showed that the expression of NLRP3, TXNIP, ASC, IL-1\u03b2, and IL-18 proteins increased in all heart failure groups compared to the control group, with the most significant increase in the low-protein diet group. Pathological examination revealed increased myocardial fibrosis in heart failure groups, which was further aggravated by low-protein diet, while probiotic intervention partially improved these pathological changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Heart failure is associated with upregulation of NLRP3 inflammasome proteins (NLRP3-TXNIP-ASC-IL-1\u03b2\/IL-18 axis) alongside gut microbiota dysbiosis; mRNA-level trends were directionally consistent but did not reach statistical significance. Low-protein diet markedly amplifies inflammasome protein expression and cardiac remodeling, while probiotic supplementation is associated with reduced NLRP3 pathway protein expression through microbiome restoration. These findings suggest NLRP3-related protein signatures as candidate biomarkers and potential therapeutic targets in heart failure, warranting further mechanistic investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1852819","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:10:24Z","timestamp":1787004624000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["NLRP3 inflammasome pathway activation is associated with cardiac remodeling, gut microbiota dysbiosis, and dietary protein restriction in a rat heart failure model: an integrative exploratory analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaopeng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1161\/CIRCRESAHA.120.315937","article-title":"Interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease","volume":"126","author":"Abbate","year":"2020","journal-title":"Circ. 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