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-1 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.