Down-regulation of LRP-1 expression by insulin in J774 murine macrophage cell line.

CESCHIN DANILO; CÁCERES LEANDRO; SÁNCHEZ MARÍA CECILIA; CHIABRANDO GUSTAVO

Pinamar

Congreso; XLI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB) 2005. X Congreso de la Panamerican Association for Biochemistry and Molecular Biology (PABMB) 2005. XX Reunión Anual de la Sociedad Argentina de Neuroquí; 2005

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

The association of different factors such as dyslipidemias, hypertension, glucose intolerance and insulin resistance increase the risk of atherosclerosis. Atherosclerosis is characterized by plaque formation and intimal hyperplasia of smooth muscle cells contributing to the risk of coronary heart disease. It is generally accepted that atherosclerotic lesions are initiated by an enhancement of LDL uptake by macrophages via specific LDL receptors and by scavenger receptor system. It has been suggested that LRP-1 (by low density lipoprotein receptor-related protein) could play key role in the development of atherosclerotic lesions by contributing to the formation of foam cells. However, how these processes are regulated remains unknown. In this work, we demonstrated that insulin down-regulates both LRP-1 protein and mARN levels in J774 murine macrophages cell line. Moreover, insulin changes the intracellular distribution of LRP-1 by modifying the vesicular traffic, which depends on this hormone. In addition, we showed that these effects were mediated by the insulin receptor involving both PKB and MEK/MAPK intracellular signalling pathways. Hence, we propose that insulin promotes LRP-1 down regulation with a consequent increased lipoprotein up-takes by scavenger receptors favouring to the formation of atherosclerotic lesions.