{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:21:42Z","timestamp":1787768502917,"version":"build-2784847793"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Atherosclerosis is characterized by the buildup of fatty plaques that thicken and stiffen arterial walls. M\u03c6s (macrophages) significantly contribute to this process through their scavenger receptor CD36 (cluster of differentiation 36). PIM1 (proviral integration site for Moloney murine leukemia virus 1) is a serine\/threonine kinase known to modulate immune responses and cell metabolism. However, its role in M\u03c6 lipid handling and atherogenesis is not well defined. This study examines the role of PIM1 in regulating CD36 expression and function in M\u03c6s during foam cell formation and atherosclerosis progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We performed in vitro studies by treating murine peritoneal M\u03c6s from\n                      <jats:italic toggle=\"yes\">Pim1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and wild-type mice with oxLDL (oxidized low-density lipoprotein). We measured CD36, PIM1, and plaque-associated proteins and mRNA levels, oxLDL binding and uptake rates, and foam cell formation. For in vivo studies, we fed myeloid-specific\n                      <jats:italic toggle=\"yes\">Pim1<\/jats:italic>\n                      -deficient (\n                      <jats:italic toggle=\"yes\">Apoe<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <jats:italic toggle=\"yes\">Lyz2<\/jats:italic>\n                      <jats:sup>Cre\/+<\/jats:sup>\n                      <jats:italic toggle=\"yes\">Pim1<\/jats:italic>\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      ) and their littermate control (\n                      <jats:italic toggle=\"yes\">Apoe<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <jats:italic toggle=\"yes\">Pim1<\/jats:italic>\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      ) mice a high-fat diet for 12 weeks. We then evaluated plaque formation in their aortic sinuses and arches.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Deletion of\n                      <jats:italic toggle=\"yes\">Pim1<\/jats:italic>\n                      in M\u03c6s reduced CD36 protein expression by up to 96.7% compared with wild-type controls. This led to a 49.6% decrease in foam cell formation and a 25.5% reduction in cellular cholesterol after oxLDL treatment. Pharmacological inhibition of PIM kinase activity in wild-type M\u03c6s also impaired oxLDL handling, with a 64.5% reduction in binding and a 57.9% reduction in uptake. Bulk RNA-sequencing revealed that\n                      <jats:italic toggle=\"yes\">Pim1<\/jats:italic>\n                      deficiency downregulated PPAR\u03b3 (peroxisome proliferator-activated receptor gamma) signaling. Treatment with a PPAR\u03b3 agonist restored CD36 levels in the\n                      <jats:italic toggle=\"yes\">Pim1<\/jats:italic>\n                      knockdown M\u03c6s, suggesting that PIM1 regulates CD36 through PPAR\u03b3. Moreover,\n                      <jats:italic toggle=\"yes\">Pim1<\/jats:italic>\n                      myeloid\u2013specific deficiency caused a 69.4% reduction in atherosclerotic plaque formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>PIM1 acts as a key upstream regulator of CD36 by enhancing PPAR\u03b3 activity in M\u03c6s. The PIM1-CD36 axis promotes oxLDL binding, uptake, and foam cell formation. Targeting the PIM1\/PPAR\u03b3\/CD36 pathway could offer new ways to modulate M\u03c6 lipid metabolism and reduce atherosclerotic plaque progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.126.324938","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:00:23Z","timestamp":1786006823000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage PIM1 Drives Atherosclerosis by Enhancing Foam Cell Formation Via CD36"],"prefix":"10.1161","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3598-894X","authenticated-orcid":true,"given":"Mirza Ahmar","family":"Beg","sequence":"first","affiliation":[{"name":"Versiti Blood Research Institute, Milwaukee, WI (M.A.B., Q.Q.L., V.C., Y.W., R.L.S., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2183-8171","authenticated-orcid":true,"given":"Quoc Quang","family":"Luu","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute, Milwaukee, WI (M.A.B., Q.Q.L., V.C., Y.W., R.L.S., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9824-4809","authenticated-orcid":true,"given":"Vaya","family":"Chen","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute, Milwaukee, WI (M.A.B., Q.Q.L., V.C., Y.W., R.L.S., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0695-3542","authenticated-orcid":true,"given":"Yaxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute, Milwaukee, WI (M.A.B., Q.Q.L., V.C., Y.W., R.L.S., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1963-505X","authenticated-orcid":true,"given":"Gang","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of 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