EARLY GLOMERULAR CHANGES IN RATS WITH DIETARY-INDUCED HYPERCHOLESTEROLEMIA

Increasing evidence suggests that lipids may be important modulators o f progressive glomerular injury. We previously reported the long-term glomerular changes in rats with dietary-induced hypercholesterolemia. In this work, we evaluated the early glomerular changes induced by hyp ercholesterolemia that precede the development of glomerulosclerosis. In cholesterol-fed rats, an early macrophage influx was observed. This was associated with an increase in glomerular size, mesangial matrix expansion, lipid deposits, and foam cell formation. Immunohistochemica l techniques showed that type IV collagen, fibronectin, and laminin we re increased in cholesterol-induced mesangial matrix accumulation. The glomerular mRNA expression of transforming growth factor-beta-1 was a lso upregulated, suggesting that transforming growth factor-beta-1 cou ld be an important mediator for mesangial matrix accumulation in hyper cholesterolemic states. The early cholesterol-induced changes in the g lomerulus are reminiscent in many respects to the process leading to g lomerulosclerosis in the vessel wall.