Lovastatin reduces glomerular macrophage influx and expression of monocyte chemoattractant protein-1 mRNA in nephrotic rats

Glomerular expression of monocyte chemoattractant protein-1 (MCP-1) and subsequent glomerular macrophage infiltration may play an important role in the development of glomerulosclerosis. Previous studies have shown that lovastatin ameliorates experimental renal disease and reduces MCP-1 expression in serum-stimulated, cultured mesangial cells. We investigated the effects of lovastatin on glomerular MCP-1 expression and macrophage infiltration in rats with puromycin aminonucleoside (PA) nephrosis, an experimental model of renal disease characterized by early macrophage infiltration. Male Sprague-Dawley rats were pretreated for 5 days with either lovastatin (4 mg/kg) or vehicle. At the end of pretreatment, the lovastatin- pretreated rats received a single IV injection of PA (50 mg/kg) and continued to receive daily lovastatin thereafter. The vehicle-pretreated rats received IV injections of either PA or saline, and continued to receive daily vehicle treatment thereafter. Ten days after PA injection, the vehicle-treated PA rats showed increased (P < 9.05) serum cholesterol (359 ± 25 mg/100 mL) and urine albumin excretion (343 ± 95 mg/24 hr), compared with the vehicle- treated control rats (61 ± 3 mg/100 mL and 2.5 ± 9.6 mg/24 hr, respectively). Serum cholesterol (193 ± 22 mg/dL) and urine albumin excretion (255 ± 68 mg/24 hr) were less in the lovastatin-treated PA rats than in the vehicle-treated PA rats. The number of glomerular macrophages, assessed as ED-1-positive cells, per glomerular profile was increased 77% in the vehicle-treated PA rats (3.3 ± 0.2) compared with the vehicle-treated control rats (1.8 ± 0.2) (P < 0.05). By contrast, the number of glomerular macrophages was not elevated in the lovastatin-treated PA rats (2.3 ± 0.2). Thus, lovastatin in vivo can attenuate glomerular macrophage infiltration. This may represent one mechanism by which lovastatin ameliorates experimental glomerular disease.