Modulation of adhesion molecules by cholesterol-lowering therapy in mononuclear cells from hypercholesterolemic patients

INTRODUCTION:Cholesterol-lowering therapy has been related with several pleiotropic effects including anti-inflammatory action in vascular endothelium; however, their influence on monocyte adhesion molecules is poorly described.AIMS:To investigate the effect of inhibitors of synthesis (statins) and absorption (ezetimibe) of cholesterol on expression of adhesion molecules L-selectin, PSGL-1, VLA-4, LFA-1, and Mac-1 in mononuclear cells in vivo and in vitro using THP-1 cells.METHODS:The influence of simvastatin (10 mg/day), ezetimibe (10 mg/day), and their combination (10 mg each/day) on mRNA expression of adhesion molecules was analyzed in peripheral blood mononuclear cells (PBMC) from hypercholesterolemics. The effects of atorvastatin, simvastatin, and ezetimibe on mRNA and protein expression of adhesion molecules were also evaluated in THP-1 cells.RESULTS:Simvastatin/ezetimibe combination, but not the monotherapies, reduced the mRNA expression of the PSGL-1, LFA-1, and Mac-1 genes in PBMC from hypercholesterolemics. Total and LDL cholesterol in serum correlated with PSGL-1 mRNA expression, whereas HDL cholesterol negatively correlated with mRNA levels of L-selectin and VLA-4 genes (P < 0.05). Plasma hsCRP was also correlated with mRNA levels of VLA-4, LFA-1, and Mac-1 (P < 0.05). Atorvastatin and simvastatin at 10 μM reduced mRNA and protein expression of L-selectin, PSGL-1, and VLA-4 in THP-1 cells (P < 0.05).CONCLUSION:Cholesterol-lowering therapy modulates gene expression of adhesion molecules in PBMC from hypercholesterolemics and THP-1 cells. Simvastatin/ezetimibe combination gives more benefits by reducing to a larger extent the expression of adhesion molecules in mononuclear cells.

Enfermedad de los cuerpos de poliglucosano del adulto: a propósito de un caso / Adult polyglucosan body disease: report of one case

La enfermedad de los cuerpos de poliglucosano del adulto es una entidad clinicopatológica establecida recientemente, de la que se han informado pocos casos en la bibliografía. Se presenta el caso adicional de un varón de 46 años de edad que falleció por un carcinoma pancreático avanzado y cuyo examen neuropotológico post mortem reveló una acumulación masiva de cuerpos de poliglucosano en toda la sustancia blanca cerebral, protuberancia anular, bulbo raquídeo, cerebelo y médula espinal compatible con enfermedad de los cuerpos de poliglucosano del adulto. Se discuten los criterios histopatológicos para el diagnóstico diferencial con otras entidades en la cuales también existen acumulación de cuerpos de poliglucosano (AU)

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