Leptin locally synthesized in carotid atherosclerotic plaques could be associated with lesion instability and cerebral emboli.
J Am Heart Assoc
; 1(5): e001727, 2012 Oct.
Article
en En
| MEDLINE
| ID: mdl-23316287
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. METHODS ANDRESULTS:
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.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Enfermedades de las Arterias Carótidas
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Factor de Necrosis Tumoral alfa
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Inhibidor 1 de Activador Plasminogénico
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Embolia Intracraneal
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Leptina
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Miocitos del Músculo Liso
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Placa Aterosclerótica
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Am Heart Assoc
Año:
2012
Tipo del documento:
Article
País de afiliación:
Israel