Hyperlipemic-very low density lipoprotein, intermediate density lipoprotein and low density lipoprotein act synergistically with serotonin on vascular smooth muscle cell proliferation

Background: Previous studies have shown that very low density lipoprotein ( VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein ( LDL) from hyperlipidemic plasma are more atherogenic than those from normal plasma. Since platelet aggregation at sites of atherosclerotic injury expo ses the cells to high concentrations of serotonin (5HT); a known mitogen fo r vascular smooth muscle cells (VSMCs), it was examined whether VLDL, IDL o r LDL from plasma of 1% cholesterol-fed rabbits can potentiate the mitogeni c effect of 5HT on VSMC. Methods: Growth arrested primary aortic VSMC in 1s t or 2nd passage were incubated with different concentrations of VLDL, IDL or LDL in the presence or absence of pertusis toxin (PTX) for 24 h followed by incubation with 5HT for 24 h. The amount of [H-3]thymidine incorporated into the DNA as well as the increase in cell number was measured. Results: Either VLDL, IDL or LDL at a concentration of 60 mu g/ml induced prolifera tion of VSMC by themselves (196, 137 or 122% increase in [H-3]thymidine inc orporation, or 122, 119 or 122% increase in cell number, respectively when compared to the control, P < 0.05). This effect on DNA synthesis was marked ly potentiated by 50 mu M 5HT to 465, 714 and 1369%, respectively. PTX reve rsed the mitogenic effect of 5HT, but not that of VLDL, IDL or LDL. Conclus ion: These results suggest that even low concentration of VLDL, IDL or LDL from hypercholesterolemic plasma may significantly potentiate the mitogenic effect of 5HT, that is released by aggregating platelets at sites of vascu lar damage. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.