{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T20:04:35Z","timestamp":1785182675400,"version":"3.55.0"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2012,9,26]]},"abstract":"\n \n Background<\/jats:italic>\n <\/jats:title>\n Unstable carotid plaques cause cerebral emboli. Leptin promotes atherosclerosis and vessel wall remodeling. We hypothesized that carotid atherosclerotic lesion instability is associated with local leptin synthesis.<\/jats:p>\n <\/jats:sec>\n \n \n Methods and Results<\/jats:italic>\n <\/jats:title>\n \n Carotid endarterectomy plaques from symptomatic (n=40) and asymptomatic patients with progressive stenosis (n=38) were analyzed for local expression of leptin, tumor necrosis factor (\n TNF<\/jats:styled-content>\n )\u2010\u03b1, and plasminogen activator inhibitor type 1. All lesions exhibited advanced atherosclerosis inclusive of thick\u2010 and thin\u2010cap fibroatheromas or lesion rupture. Symptomatic lesions exhibited more plaque ruptures and macrophage infiltration (\n P<\/jats:italic>\n =0.001 and\n P<\/jats:italic>\n =0.05, respectively). Symptomatic plaques showed preferential leptin,\n TNF<\/jats:styled-content>\n \u2010\u03b1, and plasminogen activator inhibitor type 1 transcript (\n P<\/jats:italic>\n =0.03,\n P<\/jats:italic>\n =0.04, and\n P=<\/jats:italic>\n 0.05, respectively). Leptin\n mRNA<\/jats:styled-content>\n and antigen in macrophages and smooth muscle cells were confirmed by in situ hybridization and immunohistochemistry. Plasma leptin levels were not significantly different between groups (\n P<\/jats:italic>\n =1.0), whereas\n TNF<\/jats:styled-content>\n \u2010\u03b1 was significantly increased in symptomatic patients (\n P<\/jats:italic>\n =0.006). Human aortic smooth muscle cell culture stimulated by\n TNF<\/jats:styled-content>\n \u2010\u03b1, lipopolysaccharide, or lipoteichoic acid revealed 6\u2010, 6.7\u2010, and 6\u2010fold increased secreted leptin antigen, respectively, at 72 hours (\n P<\/jats:italic>\n <0.05).\n <\/jats:p>\n <\/jats:sec>\n \n \n Conclusions<\/jats:italic>\n <\/jats:title>\n \n Neurologically symptomatic patients overexpress leptin\n mRNA<\/jats:styled-content>\n and synthesize leptin protein in carotid plaque macrophages and smooth muscle cells. Local leptin induction, presumably by\n TNF<\/jats:styled-content>\n \u2010\u03b1, could exert paracrine or autocrine effects, thereby contributing to the pathogenesis of lesion instability.\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n URL:\n www.Clinicaltrials.gov<\/jats:ext-link>\n . Unique identifier: NCT00449306.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.112.001727","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T16:46:06Z","timestamp":1369413966000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":34,"title":["Leptin Locally Synthesized in Carotid Atherosclerotic Plaques Could Be Associated With Lesion Instability and Cerebral Emboli"],"prefix":"10.1161","volume":"1","author":[{"given":"Jacob","family":"Schneiderman","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery and the Gottesdiener Vascular Biology Laboratory, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pulmonary Medicine, University Medicine Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank D.","family":"Kolodgie","sequence":"additional","affiliation":[{"name":"CVPath Institute, Inc, Gaithersburg, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naphtali","family":"Savion","sequence":"additional","affiliation":[{"name":"Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlomo","family":"Kotev\u2010Emeth","sequence":"additional","affiliation":[{"name":"Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Dardik","sequence":"additional","affiliation":[{"name":"Institute of Thrombosis and Hemostasis, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amos 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