PII SOO24-3205(98)00361-O Life zyxwvutsrqponmlkjihgfedcbaZYXWVU Seiencw, Vol. 63, zyxwvutsrqponmlkjih No. zyxwvutsrqponmlkjih 12, pp. 9951003,199S zyxwv c o p yrig ht 0 199s E!kevier science zyxwvut Inc. Printed zyxwvutsrqponmlkjihgfedcb in the USA. All rights reserwd elm-32Qy98$19.00 t .oo PROLIFERATIVE EFFECTS OF OXIDIZED LOW-DENSITY LIPOPROTEIN ON VASCULAR SMOOTH MUSCLE CELLS: ROLE OF DIETARY HABITS Tuula A. LXhteenmakiki*, Riitta Korpela*, **, Matti J. Tikkanen***, Kirsi Karjala*, Juha Laakso*, Erkka Solatunturi’ and Heikki Vapaatalo* * Institute of Biomedicine, Department of Pharmacology and Toxicology, P.O. Box 8, FIN-00014 University of Helsinki, Finland. ** Foundation for Nutrition Research, P.O. Box 390, FIN-00101 Helsinki, Finland. *** University Central Hospital of Helsinki, Department of Medicine, Haartmaninkatu 4, FIN-00290 Helsinki, Finland. (Received in final form July 6, 1998) Summary The effects were studied of native, partially-oxidized and totally-oxidized human low-density lipoprotein (LDL) on the proliferation of cultured rat aortic smooth muscle cells (VSMC), measured as an altered DNA synthesis. The LDL was obtained from three different human long-term diet groups (a control diet rich in saturated fats, a vegetarian diet, and a fish diet). The oxidized LDLs were prepared by oxidizing the LDL with copper sulfate. The DNA synthesis was measured by [3H]-thymidine incorporation into the DNA. The partially-oxidized LDL was the most potent promoter of DNA synthesis compared to the native or totally-oxidized LDL of the same diet group. The partially-oxidized LDL had a true mitogenic effect in the absence of exogenous growth factors. The native and totally-oxidized LDL induced a significant increase in DNA synthesis, if they were obtained from the fish diet group. This study suggests an enhanced proliferative effect of partially- oxidized LDL on VSMC growth. Key Words: low-density lipoprotein, oxidation, vascular smooth muscle cells, diet Low density lipoprotein (LDL), the major cholesterol carrier in human plasma, is regarded as one of the major risk factors of atherosclerosis (1). The proliferation of vascular smooth muscle cells (VSMC) and migration to the intima of the arterial wall are critical events in the development of atherogenesis and subsequently in the pathogenesis of cardiovascular diseases. Previous reports have been contradictory, showing both mitogenic and nomnitogenic effects of LDL on VSMC Corresponding author: T.A. Lahteemnlki, M.Sci., Institute of Biomedicine, Department of Pharmacology and Toxicology, P.O. Box 8, FIN-00014 University of Helsinki, Finland. Phone: +358-9-191 8275; Fax: +358-9-191 8288; E-Mail: tuula.lahteemnaki@helsinki.fi.