Fate and Function of Oxidized Phospholipids in Aortic Smooth Muscle Cells. Biochemical and Biophysical Aspects (FWF-P14714)

Interactions of oxidized lipoproteins with the cells of the arterial wall induce and influence the progress of atherosclerosis. Accumulation of foam cells and excessive intimal growth of smooth muscle cells alternating with focal massive cell death are characteristics typical of the atherosclerotic lesion. Our studies focus on the products of phospholipid oxidation and the specific cellular effects of these compounds originating from the individual phospholipid classes, subclasses and species. We synthesized defined oxidized phosphatidylcholines which are typically found in biological samples. The respective compounds contain long hydrocarbon chains in position sn-1 and short polar acyl, carboxyacyl or aldehydoacyl residues in position sn-2 of the glycerol backbone. Oxidized phosphatidylcholines induce proliferation and apoptosis of cultured vascular smooth muscle cells in a specific way, depending on cell line, lipid concentration and exposure time. They activate intracellular signalling components which are involved in cell growth and death. Fluorescence microscopic studies on labeled lipid analogs revealed that the short-chain phosphatidylcholines are easily transferred from the aqueous phase into the cell plasma membrane and rapidly spread throughout the cells. Under these circumstances, it can be envisioned that the biologically active compounds may interfere directly with the signalling components inside the cells which finally decide about cell growth or death.