RESUMEN

BACKGROUND AND AIMS: Stabilin-1 (STAB1) is a scavenger receptor expressed on alternatively activated macrophages and sinusoidal endothelial cells. Its ligands include oxidized low-density lipoprotein (LDL) and the extracellular matrix glycoprotein SPARC and it is present in both human and murine atherosclerotic lesions. We aimed to investigate the effect of specific deletion of STAB1 in bone marrow-derived cells, including macrophages on atherosclerotic lesion formation in mice. METHODS: Lethally irradiated hypercholesterolemic LDL receptor knockout mice received either wildtype (WT) or STAB1 knockout (STAB1 KO) bone marrow. Bone marrow transplanted mice were fed a Western-type diet for 9 weeks to induce atherosclerotic lesion formation. RESULTS: Interestingly, LDL receptor knockout mice reconstituted with STAB1 KO bone marrow showed increased body weight gain (two-way ANOVA: p < 0.001) and larger white adipocyte cell sizes (43% increase in cell area; p < 0.05) as compared to WT bone marrow transplanted mice, which correlated positively (r = 0.82; p < 0.001). This was paralleled by a significant increase in white adipose tissue relative mRNA expression levels of the adipokine leptin (+94% p < 0.05). Despite these changes, no differences in serum lipid levels, the extent of in vivo macrophage foam cell formation or circulating leukocyte concentrations were observed. Moreover, the size and composition of atherosclerotic lesions was not different between the two experimental groups. CONCLUSIONS: Bone marrow-specific Stabilin-1 deletion does not affect the susceptibility for atherosclerosis in mice. However, the increased body weight gain and adipocyte cell size highlight a potential role for leukocyte STAB1 in the development of metabolic disorders.

Asunto(s)

Enfermedades de la Aorta/metabolismo , Aterosclerosis/metabolismo , Moléculas de Adhesión Celular Neuronal/deficiencia , Células Espumosas/metabolismo , Receptores de LDL/deficiencia , Adipocitos Blancos/metabolismo , Adipocitos Blancos/patología , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/patología , Animales , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/patología , Aterosclerosis/etiología , Aterosclerosis/genética , Aterosclerosis/patología , Moléculas de Adhesión Celular Neuronal/genética , Dieta Occidental , Modelos Animales de Enfermedad , Células Espumosas/patología , Hipercolesterolemia/complicaciones , Hipercolesterolemia/genética , Leptina/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Placa Aterosclerótica , Receptores de LDL/genética , Aumento de Peso