{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:59:16Z","timestamp":1790189956717,"version":"4.1.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      Hutchinson-Gilford progeria syndrome is an accelerated aging disorder characterized by numerous symptoms, including early onset atherosclerosis, myocardial infarctions, and strokes. Hutchinson-Gilford progeria syndrome is caused by mutations in\n                      <jats:italic toggle=\"yes\">LMNA<\/jats:italic>\n                      that lead to expression of an internally truncated, farnesylated prelamin A variant called progerin, which induces loss of vascular smooth muscle cells. Some studies have also reported that accumulation of full-length farnesylated prelamin A, which is normally completely processed to mature nonfarnesylated lamin A, can also drive vascular pathology during physiological aging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      To assess the effects of prelamin A expression on atherosclerosis and aortic media vascular smooth muscle cells, we used\n                      <jats:italic toggle=\"yes\">Lmna<\/jats:italic>\n                      <jats:sup>L648R\/L648R<\/jats:sup>\n                      mice that express a prelamin A variant with a lysine to arginine point mutation that prevents its processing to mature lamin A. We previously demonstrated bone defects, reduced body fat, and low body mass in these mice, similar to Hutchinson-Gilford progeria syndrome model mice. To determine if prelamin A expression has an impact on atherosclerotic plaques, we crossed\n                      <jats:italic toggle=\"yes\">Lmna<\/jats:italic>\n                      <jats:sup>L648R\/L648R<\/jats:sup>\n                      mice to low-density lipoprotein receptor-deficient\n                      <jats:italic toggle=\"yes\">Ldlr<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice that develop hyperlipidemia on a high-fat diet.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Atherosclerotic plaque lesion area and necrotic core area were not different in hyperlipidemic\n                      <jats:italic toggle=\"yes\">Lmna<\/jats:italic>\n                      <jats:sup>L648R\/L648R<\/jats:sup>\n                      mice that expressed only prelamin A, and no mature lamin A, compared with hyperlipidemic\n                      <jats:italic toggle=\"yes\">Lmna<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">+\/+<\/jats:italic>\n                      <\/jats:sup>\n                      mice that expressed only fully processed mature lamin A and no prelamin A. Additionally, exclusive prelamin A expression did not result in loss of aortic vascular smooth muscle cells or adventitial thickening in hyperlipidemic\n                      <jats:italic toggle=\"yes\">Lmna<\/jats:italic>\n                      <jats:sup>L648R\/L648R<\/jats:sup>\n                      mice with atherosclerosis at 28 weeks of age. Indeed, aortic vascular smooth muscle remained normal in older\n                      <jats:italic toggle=\"yes\">Lmna<\/jats:italic>\n                      <jats:sup>L648R\/L648R<\/jats:sup>\n                      mice at 52 weeks of age. There were no differences in proliferation or apoptosis of aortic media cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      In contrast to the prelamin A variant progerin expressed in Hutchinson-Gilford progeria syndrome, prelamin A does not appear to cause vascular smooth muscle loss, promote atherosclerosis, or drive vascular aging in\n                      <jats:italic toggle=\"yes\">Lmna<\/jats:italic>\n                      <jats:sup>L648R\/L648R<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.126.324400","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:00:43Z","timestamp":1778749243000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Prelamin A in an\n                    <i>Lmna<\/i>\n                    <sup>L648R\/L648R<\/sup>\n                    Mouse Model Does Not Promote Atherosclerosis or Vascular Smooth Muscle Loss"],"prefix":"10.1161","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5461-7469","authenticated-orcid":true,"given":"Yuexia","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medicine (Y.W., L.C.J., C.\u00d6., G.K., H.J.W.), Vagelos College of Physicians and Surgeons, Columbia University, New York."},{"name":"Department of Pathology and Cell Biology (Y.W., C.\u00d6., H.J.W.), Vagelos College of Physicians and Surgeons, Columbia University, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leroy C.","family":"Joseph","sequence":"additional","affiliation":[{"name":"Department of Medicine (Y.W., L.C.J., C.\u00d6., G.K., H.J.W.), Vagelos College of Physicians and Surgeons, Columbia University, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"\u00d6stlund","sequence":"additional","affiliation":[{"name":"Department of Medicine (Y.W., L.C.J., C.\u00d6., G.K., H.J.W.), Vagelos College of Physicians and Surgeons, Columbia University, New York."},{"name":"Department of Pathology and Cell Biology (Y.W., C.\u00d6., H.J.W.), Vagelos College of Physicians and Surgeons, Columbia University, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kuriakose","sequence":"additional","affiliation":[{"name":"Department of Medicine (Y.W., L.C.J., C.\u00d6., G.K., H.J.W.), Vagelos College of Physicians and Surgeons, Columbia University, New 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