{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:09:42Z","timestamp":1784225382705,"version":"3.55.0"},"reference-count":67,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2026,7,17]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Cigarette smoking (CS) is a major risk factor for cardiovascular disease through chronic inflammation. While its pulmonary effects are well established, the mechanisms linking lung inflammation to vascular injury remain unclear. Because neutrophils are early responders to CS-induced inflammation, we hypothesized that they drive systemic myelopoiesis and vascular inflammation via alarmin release.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Wild-type mice were exposed to inhaled CS or orally administered cigarette smoke extract. Immune cell composition in lung, bronchoalveolar lavage fluid, blood, spleen, and bone marrow was assessed by flow cytometry. Hematopoietic stem and progenitor cell proliferation, reactive oxygen species production, and S100A8\/A9 (S100 calcium-binding protein A8\/A9) release were quantified. Atherosclerosis progression was evaluated in\n                      <jats:italic toggle=\"yes\">\n                        Ldlr\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      (low-density lipoprotein receptor-deficient) mice fed a Western diet and treated with cigarette smoke extract. To define the role of neutrophil-derived S100A8\/A9, bone marrow transplantation was performed using\n                      <jats:italic toggle=\"yes\">S100a9<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      or wild-type donors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      CS exposure increased circulating monocytes and neutrophils through enhanced bone marrow myelopoiesis and elevated reactive oxygen species-dependent S100A8\/A9 release. Oral cigarette smoke extract reproduced these effects, indicating direct activation of neutrophils independent of pulmonary inflammation or lipid changes. In\n                      <jats:italic toggle=\"yes\">Ldlr<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice, cigarette smoke extract accelerated atherosclerosis by promoting infiltration of inflammasome-primed neutrophils, increasing IL-1\u03b2 (interleukin 1 beta) release, and impairing macrophage efferocytosis. Hematopoietic\n                      <jats:italic toggle=\"yes\">S100a9<\/jats:italic>\n                      deletion normalized myelopoiesis and reduced vascular inflammation and plaque burden.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Ingested CS components directly activate neutrophils to release S100A8\/A9, triggering myelopoiesis and vascular inflammation. These findings reveal that tobacco\u2019s cardiovascular toxicity extends beyond inhalation, implicating oral exposure as a driver of systemic inflammation and atherogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.125.327714","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:00:59Z","timestamp":1781082059000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammasome-Primed Neutrophils Aggravate Atherosclerosis in Cigarette Smoking"],"prefix":"10.1161","volume":"139","author":[{"given":"Dipanjan","family":"Chattopadhyay","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular Section, University of Oklahoma Health Sciences Center (D.C., N.N., K.P.M., B.K., A.D., R.S., 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P.R.N.)."},{"name":"Now with Department of Biotechnology, School of Biosciences and Technology, SRM Institute of Science and Technology (SRMIST), Tiruchirappalli, India (B.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8458-9785","authenticated-orcid":true,"given":"Krishna P.","family":"Maremanda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular Section, University of Oklahoma Health Sciences Center (D.C., N.N., K.P.M., B.K., A.D., R.S., P.R.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8518-9751","authenticated-orcid":true,"given":"Babunageswararao","family":"Kanuri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular Section, University of Oklahoma Health Sciences Center (D.C., N.N., K.P.M., B.K., A.D., R.S., 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