RESUMO
BACKGROUND: Prior studies have suggested a central role for cellular adhesion molecules (CAMs) in the pathophysiology and symptoms of atherosclerotic carotid plaques (CPs). OBJECTIVE: This study examined the role of CAMs in symptom generation in patients with advanced carotid artery disease. METHODS: Ninety-two consecutive patients underwent carotid endarterectomy, six for both sides (54 symptomatic and 41 asymptomatic CPs). Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and E-selectin were immunostained in fresh-frozen CP specimens and examined semiquantitatively in the endothelium and intima-media. Plasma concentrations of soluble ICAM-1 and sVCAM-1 were analyzed by ELISA. RESULTS: Endothelial expression of ICAM-1, VCAM-1, P-selectin, and E-selectin did not differ between symptomatic and asymptomatic CPs, but endothelial ICAM-1 was associated with serum sensitized C-reactive protein levels (p = 0.026). However, there was less ICAM-1 expression in the intima-media of the symptomatic CPs (p = 0.022), and there was a similar, but nonsignificant tendency for VCAM-1. Soluble ICAM-1 and soluble VCAM-1 were not associated with the symptom status. CONCLUSIONS: In contrast to earlier studies, it was found that symptomatic carotid disease is not associated with increased expression of adhesion molecules in the endothelium of advanced carotid plaques or in circulation. Rather, there was less expression of adhesion molecules in the intima-media of symptomatic carotid plaques.
Assuntos
Amaurose Fugaz/etiologia , Estenose das Carótidas/metabolismo , Moléculas de Adesão Celular/biossíntese , Ataque Isquêmico Transitório/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Amaurose Fugaz/metabolismo , Proteína C-Reativa/análise , Estenose das Carótidas/complicações , Estenose das Carótidas/patologia , Estenose das Carótidas/cirurgia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/fisiologia , Selectina E/biossíntese , Selectina E/genética , Endarterectomia das Carótidas , Endotélio Vascular/metabolismo , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Regulação da Expressão Gênica , Humanos , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/genética , Ataque Isquêmico Transitório/metabolismo , Masculino , Pessoa de Meia-Idade , Selectina-P/biossíntese , Selectina-P/genética , Método Simples-Cego , Solubilidade , Acidente Vascular Cerebral/metabolismo , Túnica Íntima/metabolismo , Túnica Média/metabolismo , Molécula 1 de Adesão de Célula Vascular/biossíntese , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
Lipid droplets and membrane material are produced in the extracellular matrix of the arterial intima during atherogenesis. Both in vitro and in vivo experimentation suggests that fusion of modified LDL particles leads to formation of such lipid droplets. Here we applied proton NMR spectroscopy to probe surface phospholipids phosphatidylcholine (PC) and sphingomyelin (SM) of LDL particles during proteolytic degradation of apolipoprotein B-100 (apoB-100). Initiation of apoB-100 degradation was accompanied by the abruptly increased intensity of the choline -N(CH(3))(3) resonance of PC molecules, indicating disruption of their interactions with apoB-100. However, subsequent particle fusion was accompanied by a steady decrease in the intensity of the choline resonances of both PC and SM. Electron microscopy of the proteolyzed LDL revealed irregularly shaped multilamellar membranes attached to aggregates of fused particles. This suggests formation of membrane material with low hydration, in which some of the atomic motions are hindered. Characterization of the behavior of the surface lipids of LDL particles during apoB-100 degradation and other types of LDL modification will aid in understanding molecular mechanisms leading to fusion and generation of multilamellar membrane material in the arterial intima during atherogenesis.
