The Interaction of Lp(A) with Liver Cells: Implications for Lipid Lowering Therapy

There is now general agreement that Lp(a) is one of the most atherogenic lipoproteins. Concerning its pathophysiology, there are currently two theories discussed: i) L?(a) interferes with Fibrinolysis in many ways, notably by inhibiting the t-PA mediated activation of plasminogen, ii) Lp(a) or chemically modified Lp(a) is taken up by the scavenger pathway, leading to foam cell formation and cholesterol accumulation in the vessel wall. Little is known today about the nascent form of Lp(a) and its assembly. From in vivo turnover studies it appears that Lp(a) is secreted directly from the liver. The site of Lp(a) catabolism is completely in the dark. In vitro studies suggest that Lp(a) binds to the LDL-receptor; whether or not this is also true in vivo is subject of intensive investigations. In order to shed some light into this question, the interaction of Lp(a) with cultivated hepatoma cells has been investigated. Other than with fibroblasts, there seems to be only low affinity, non-saturable binding of Lp(a) to Hep-G2 and He?-3B cells. Preincubation of hepatoma cells with HMG-CoA reductase inhibitors increases Lp(a) binding only slightly. Preincubation of hepatoma cells with Lp(a) however increases markedly high affinity LDL-binding. The Lp(a) triggerd LDL-binding however is not followed by an increase in LDL internalization degradation, or a decrease of cholesterol biosynthesis.