[Atherogenic lipoprotein(a) as a progression factor in glomerular diseases: studies in cultured rat mesangial cells]

Lipoprotein abnormalities are a risk factor for atherosclerotic disease and considered to accelerate glomerular injury in kidney disease. Serum levels of Lp(a) are elevated in patients with nephrotic syndrome and Lp(a) deposits are found in diseased glomeruli. Since mesangial hypercellularity is a prominent feature in a variety of glomerular diseases, we studied the effects of Lp(a) on proliferation of cultured rat mesangial cells. DNA synthesis was stimulated in cells incubated in the presence of Lp(a) as were the mRNA levels for c-fos and c-myc, two "early genes" that serve as transcription factors. Lp(a) also accelerated cell growth by 42 +/- 6% compared to control cells. Increased DNA synthesis was partially blunted, when cells were incubated with Lp(a) in the presence of oxygen radical scavengers CAT and SOD. We conclude that Lp(a) abnormalities are likely to contribute to glomerular injury in kidney disease. The mechanism by which Lp(a) alters the proliferation rate of mesangial cells involves the formation of reactive oxygen species.