Open AccessLeptin Locally Synthesized in Carotid Atherosclerotic Plaques Could Be Associated With Lesion Instability and Cerebral Emboli
Author(s) -
Schneiderman Jacob,
Schaefer Katrin,
Kolodgie Frank D.,
Savion Naphtali,
KotevEmeth Shlomo,
Dardik Rima,
Simon Amos J.,
Halak Moshe,
Pariente Clara,
Engelberg Isaac,
Konstantinides Stavros,
Virmani Renu
Publication year - 2012
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.112.001727
Subject(s) - leptin , medicine , lesion , plasminogen activator , autocrine signalling , pathogenesis , endocrinology , pathology , receptor , obesity
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.Methods and 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. Clinical Trial Registration URL: www.Clinicaltrials.gov . Unique identifier: NCT00449306.