{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:40:35Z","timestamp":1793911235434,"version":"4.8.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypertension-induced pressure overload is a major driver of chronic heart failure (CHF) and is accompanied by persistent sterile inflammation. However, the upstream mechanisms linking mechanical stress to inflammasome activation across disease stages remain insufficiently defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize the stage-specific role of the extracellular ATP\u2013P2X7\u2013NLRP3 inflammasome axis in pressure overload\u2013induced CHF and to assess its therapeutic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A transverse aortic constriction (TAC) mouse model was established and followed longitudinally using hemodynamic assessment and echocardiography. Extracellular ATP signaling, P2X7 activation, NLRP3 inflammasome priming and assembly, downstream effector responses, histologic remodeling, and inflammatory cell infiltration were evaluated across disease stages. Causality was tested using pharmacologic inhibition (P2X7 antagonism and the NLRP3 inhibitor MCC950) and genetic deletion of Nlrp3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pressure overload induced stage-dependent amplification of extracellular ATP\u2013P2X7 signaling, accompanied by progressive activation of NLRP3 inflammasome pathways. These changes were associated with macrophage accumulation, worsening fibrosis, and declining cardiac function. Pharmacologic or genetic disruption of the ATP\u2013P2X7\u2013NLRP3 axis attenuated inflammasome signaling, reduced adverse remodeling, and improved cardiac structure and function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Extracellular ATP\u2013P2X7 signaling is an upstream driver of NLRP3 inflammasome activation during pressure overload\u2013induced CHF. The ATP\u2013P2X7\u2013NLRP3 axis may therefore represent a stage-informed and therapeutically actionable target for hypertension-related CHF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1780542","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:34:51Z","timestamp":1782920091000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The role of the NLRP3 inflammasome in hypertension-related chronic heart failure and its potential therapeutic targets"],"prefix":"10.3389","volume":"17","author":[{"given":"Feilong","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Cardiology, Xinhua Hospital Affiliated to Dalian University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Xinhua Hospital Affiliated to 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