{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:00:45Z","timestamp":1790424045933,"version":"4.1.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,5,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Marfan syndrome (\n              <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>\n              ) is a genetically transmitted connective tissue disorder characterized by aortic root dilatation, dissection, and rupture. Molecularly,\n              <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>\n              pathological features have been shown to be driven by increased angiotensin\n              <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n              in the aortic wall. Using an angiotensin\n              <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n              \u2013driven aneurysm mouse model, we have recently demonstrated that local inhibition of leptin activity restricts aneurysm formation in the ascending and abdominal aorta. As we observed de novo leptin synthesis in the ascending aortic aneurysm wall of patients with MFS, we hypothesized that local counteracting of leptin activity in\n              <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>\n              may also prevent aortic cardiovascular complications in this context.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:italic>Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>C1039G\/+<\/jats:italic>\n              <\/jats:sup>\n              mice underwent periaortic application of low\u2010dose leptin antagonist at the aortic root. Treatment abolished medial degeneration and prevented increase in aortic root diameter (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). High levels of leptin, transforming growth factor \u03b21, Phosphorylated Small mothers against decapentaplegic 2, and angiotensin\u2010converting enzyme 1 observed in saline\u2010treated\n              <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>\n              mice were downregulated in leptin antagonist\u2013treated animals (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001, and\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001, respectively). Leptin and angiotensin\u2010converting enzyme 1 expression levels in left ventricular cardiomyocytes were also decreased (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and coincided with prevention of left ventricular hypertrophy and aortic and mitral valve leaflet thickening (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01 and\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05, respectively) and systolic function preservation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Local, periaortic application of leptin antagonist prevented aortic root dilatation and left ventricular valve remodeling, preserving left ventricular systolic function in an\n              <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>\n              mouse model. Our results suggest that local inhibition of leptin may constitute a novel, stand\u2010alone approach to prevent\n              <jats:styled-content style=\"fixed-case\">MFS<\/jats:styled-content>\n              aortic root aneurysms and potentially other similar angiotensin\n              <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n              \u2013driven aortic pathological features.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.014761","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T09:05:26Z","timestamp":1588842326000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Localized Antileptin Therapy Prevents Aortic Root Dilatation and Preserves Left Ventricular Systolic Function in a Murine Model of Marfan 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