{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T19:33:56Z","timestamp":1790451236457,"version":"4.1.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"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. Immunol."],"abstract":"<jats:p>Obesity drives cardiovascular disease primarily through chronic meta-inflammation, yet the precise molecular convergence linking nutrient excess to sustained NLRP3 inflammasome activation in macrophages has remained unclear. Obesity induces inhibitory phosphorylation of SAMHD1, resulting in cytosolic dNTP accumulation, mitochondrial import through SLC25 transporters, uncontrolled mtDNA synthesis and oxidation, and consequent NLRP3 hyperactivation. This SAMHD1\u2013dNTP\u2013mtDNA\u2013NLRP3 axis is supported by emerging evidence as a potential upstream checkpoint that may set macrophage inflammatory tone and may contribute to three major manifestations of obesity-associated cardiovascular pathology: accelerated atherosclerosis, diastolic dysfunction in obesity cardiomyopathy, and exaggerated ischemia\u2013reperfusion injury. Integration of human macrophage data, atherosclerotic plaque biology, and mitochondrial transport mechanisms reveals actionable therapeutic nodes at selective SLC25 inhibition, SAMHD1-preserving kinase modulation, and mitochondria-targeted antioxidants that act at the metabolic initiation phase rather than downstream effector cascades. Nucleotide metabolism reprogramming thereby provides a plausible framework that may help address a long-standing mechanistic gap in immunometabolism and opens a new class of precision interventions that could address the root cause of obesity-driven cardiovascular risk.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1829718","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:32:29Z","timestamp":1777005149000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Nucleotide metabolism reprogramming in obesity-associated cardiovascular inflammation: a new perspective"],"prefix":"10.3389","volume":"17","author":[{"given":"Taoming","family":"Qian","sequence":"first","affiliation":[{"name":"Graduate School, Heilongjiang University of Chinese Medicine","place":["Harbin, 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