title: Leptin locally synthesized in carotid atherosclerotic plaques could be associated with lesion instability and cerebral emboli.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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 (TNF)-α, and plasminogen activator inhibitor type 1. All lesions exhibited advanced atherosclerosis inclusive of thick- and thin-cap fibroatheromas or lesion rupture. Symptomatic lesions exhibited more plaque ruptures and macrophage infiltration (P=0.001 and P=0.05, respectively). Symptomatic plaques showed preferential leptin, TNF-α, and plasminogen activator inhibitor type 1 transcript (P=0.03, P=0.04, and P=0.05, respectively). Leptin mRNA 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 (P=1.0), whereas TNF-α was significantly increased in symptomatic patients (P=0.006). Human aortic smooth muscle cell culture stimulated by TNF-α, lipopolysaccharide, or lipoteichoic acid revealed 6-, 6.7-, and 6-fold increased secreted leptin antigen, respectively, at 72 hours (P<0.05).
  
  
  CONCLUSIONS
  Neurologically symptomatic patients overexpress leptin mRNA and synthesize leptin protein in carotid plaque macrophages and smooth muscle cells. Local leptin induction, presumably by TNF-α, could exert paracrine or autocrine effects, thereby contributing to the pathogenesis of lesion instability.
  
  
  BACKGROUND
  URL: www.Clinicaltrials.gov. Unique identifier: NCT00449306.
authors: Department of Vascular Surgery and the Gottesdiener Vascular Biology Laboratory, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel. jschneid72@yahoo.com
authors: Jacob
authors: J
authors: Schneiderman
authors: Katrin
authors: K
authors: Schaefer
authors: Frank D
authors: FD
authors: Kolodgie
authors: Naphtali
authors: N
authors: Savion
authors: Shlomo
authors: S
authors: Kotev-Emeth
authors: Rima
authors: R
authors: Dardik
authors: Amos J
authors: AJ
authors: Simon
authors: Moshe
authors: M
authors: Halak
authors: Clara
authors: C
authors: Pariente
authors: Isaac
authors: I
authors: Engelberg
authors: Stavros
authors: S
authors: Konstantinides
authors: Renu
authors: R
authors: Virmani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020766:Intracranial Embolism / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha
keywords: atherosclerosis; leptin; macrophages; smooth muscle cells; tumor necrosis factor-α