Mesangial expansion associated with glomerular endothelial cell activation and macrophage recruitment is developing in hyperlipidaemic apoE null mice

Background. Lipids are involved in the onset and/or the progression of renal diseases. ApoE null mice are hyperlipidaemic and thus represent an experimental model for the study of the effect of severe hypercholesterolaemia on renal lesion development. Methods. ApoE null mice were studied at 6 weeks of age fed a normal chow, after 20 weeks on a normal chow (mild hypercholesterolaemia), or a 0.15% cholesterol Western diet (WD; severe hypercholesterolaemia). Age- and diet-matched C57/B6 mice were used as controls. Glomerular structure was assessed by histology, electron microscopy and computerized morphometry. Glomerular macrophage recruitment and alpha-smooth-muscle actin, PCNA, VCAM-I and MHC class II (I-A(b)) expressions were assessed by immunohistochemistry. Results. ApoE null mice fed the WD developed mesangial expansion characterized by an increase in mesangial area (P < 0.05 vs C57BL/6 mice at 20 weeks). In apoE null mice, this was accompanied by a glomerular inflammatory process as demonstrated by (i) the presence of foam cells, (ii) macrophage recruitment, (iii) a higher expression of the I-A(b) activation marker and (iv) endothelial-cell activation (VCAM-1 expression in 100% of glomeruli and electron microscopy showing cytoplasmic foldings protruding in the capillary lumina). This might explain why we also observed blood monocytes adhering to glomerular endothelial cells. Conclusions. In apoE null mice, severe hyperlipidaemia leads to glomerular injury characterized by glomerular endothelial cell activation and macrophage recruitment.