Effects of low-density lipoproteins on mesangial cell growth and viability in vitro

Recent animal studies suggest that abnormal lipid metabolism may play a role in the pathogenesis of glomerulosclerosis. In order to define mechanisms whereby lipoproteins could contribute to glomerular injury, the effect of Low-density lipoprotein (LDL) concentration on the proliferation of rat mesangial cells was studied in vitro. Human LDL was added to culture medium that had been rendered otherwise lipid free and proliferation rate was estimated by measuring incorporation of 3H-thymidine. When compared to standard medium, LDL-enriched medium stimulated cell division when present in protein concentrations of between 10 and 100 micrograms/ml. At greater concentrations (more than 200 micrograms/ml), cell proliferation was inhibited and above 500 micrograms/ml cells sustained visible morphological injury when assessed under phase contrast microscopy. Estimation of 51Cr release from prelabelled cells confirmed that LDL was cytotoxic in these greater concentrations. A similar pattern of proliferation and toxicity has been observed in vascular smooth muscle cell cultures over a corresponding range of LDL concentrations. These results strengthen the analogy between glomerulosclerosis and atherosclerosis and provide further evidence that lipoproteins may contribute directly to glomerular scarring.