{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:59:15Z","timestamp":1790189955847,"version":"4.1.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,7]]},"abstract":"\n BACKGROUND:<\/jats:title>\n \n Clonal hematopoiesis (CH) is an age-associated condition common in the elderly that arises when hematopoietic stem cells acquire somatic mutations in an assortment of genes, most commonly\n DNMT3A<\/jats:italic>\n ,\n TET2<\/jats:italic>\n ,\n ASXL1<\/jats:italic>\n ,\n PPM1D<\/jats:italic>\n , and\n JAK2.<\/jats:italic>\n CH is associated with increased coronary artery disease and all-cause mortality. Epidemiological studies have revealed that different CH driver mutations are associated with unique outcomes.\n PPM1D<\/jats:italic>\n CH is more prevalent in patients following radiation and cytotoxic therapy.\n PPM1D<\/jats:italic>\n CH has been strongly associated with coronary artery disease, peripheral artery disease, and all-cause mortality. However, it is unclear if this relationship is causative.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n \n We tested the ability of\n Ppm1d<\/jats:italic>\n mutations to promote atherosclerosis in mice. To model\n Ppm1d<\/jats:italic>\n CH, we transplanted a mixture of 20% bone marrow from mice expressing\n Ppm1d T476<\/jats:italic>\n * truncation mutation under the control of an\n Scl-Cre<\/jats:italic>\n and 80% wild-type bone marrow into\n Ldlr<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n recipient mice and subjected them to atherosclerosis studies. In parallel,\n Scl-Cre<\/jats:italic>\n -driven\n Ppm1d T476<\/jats:italic>\n * mutations were introduced into\n Apoe<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice for atherosclerosis studies. To examine the interaction between DNA damage and\n Ppm1d<\/jats:italic>\n , we transplanted bone marrow with\n Ppm1d<\/jats:italic>\n mutations restricted to monocyte\/macrophage or pan-hematopoietic expression of\n Ppm1d T476<\/jats:italic>\n * into\n Ldlr<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice. Cisplatin was administered after the establishment of atherosclerosis, and lesion burden and inflammasome activation were quantified.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n We found that in vitro\n Ppm1d<\/jats:italic>\n mutant macrophages have increased AIM2 (absent in melanoma 2) inflammasome activation and increased inflammasome activation in response to cisplatin. However, in vivo, we found no evidence of elevated inflammasome activation in plaques. Across both\n Ldlr<\/jats:italic>\n and\n Apoe<\/jats:italic>\n knockout models, hematopoietic\n Ppm1d<\/jats:italic>\n mutations did not promote atherosclerosis. Furthermore,\n Ppm1d<\/jats:italic>\n mutations did not exacerbate atherosclerosis following administration of cisplatin.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n \n These findings indicate that in murine models,\n Ppm1d<\/jats:italic>\n mutations are not sufficient to promote atherosclerosis, suggesting that the epidemiological association between\n PPM1D<\/jats:italic>\n CH and coronary artery disease may not be due to changes in plaque development.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/atvbaha.125.323733","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T09:00:18Z","timestamp":1779354018000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Ppm1d<\/i>\n Clonal Hematopoiesis Does Not Promote Atherosclerosis in Murine Models"],"prefix":"10.1161","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6748-501X","authenticated-orcid":true,"given":"Cesar","family":"De Jeronimo Diaz","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute (C.D.J.D., H.L., A.L.G., M.L., A.K., G.Q., E.L., T.P.F.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0951-3933","authenticated-orcid":true,"given":"Huajun","family":"Liao","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (C.D.J.D., H.L., A.L.G., M.L., A.K., G.Q., E.L., T.P.F.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-3494","authenticated-orcid":true,"given":"Brian","family":"Hardaway","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, NY (B.H., S.A., A.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6350-5121","authenticated-orcid":true,"given":"Linke","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical and Translational Epidemiology Unit (L.L., Z.Y.), Massachusetts General Hospital, Boston."},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA (L.L., Z.Y., P.G.M., B.L.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Lu","family":"Gan","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (C.D.J.D., H.L., A.L.G., M.L., A.K., G.Q., E.L., T.P.F.), University of California, San Francisco."},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Berlin, Germany (A.L.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2458-1658","authenticated-orcid":true,"given":"Mandy","family":"Liu","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (C.D.J.D., H.L., A.L.G., M.L., A.K., G.Q., E.L., T.P.F.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Kim","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (C.D.J.D., H.L., A.L.G., M.L., A.K., G.Q., E.L., T.P.F.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4458-7579","authenticated-orcid":true,"given":"Grace","family":"Qian","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (C.D.J.D., H.L., A.L.G., M.L., A.K., G.Q., E.L., T.P.F.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Abramowicz","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, NY (B.H., S.A., A.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edithe","family":"Lam","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute (C.D.J.D., H.L., A.L.G., M.L., A.K., G.Q., E.L., T.P.F.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5996-4099","authenticated-orcid":true,"given":"Zian H.","family":"Tseng","sequence":"additional","affiliation":[{"name":"Division of Cardiology (Z.H.T.), University of California, San Francisco."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4634-8830","authenticated-orcid":true,"given":"W. 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