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 exposes the cells to high concentrations of serotonin (5HT), a known mitogen for vascular smooth muscle cells (VSMCs), it was examined whether VLDL, IDL or LDL from plasma of 1% cholesterol-fed rabbits can potentiate the mitogenic effect of 5HT on VSMC.


METHODS
Growth arrested primary aortic VSMC in 1st 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 [3H]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 microg/ml induced proliferation of VSMC by themselves (196, 137 or 122% increase in [3H]thymidine incorporation, or 122, 119 or 122% increase in cell number, respectively when compared to the control, P<0.05). This effect on DNA synthesis was markedly potentiated by 50 microM 5HT to 465, 714 and 1369%, respectively. PTX reversed the mitogenic effect of 5HT, but not that of VLDL, IDL or LDL.


CONCLUSIONS
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 vascular damage.
Koba
S
S
Department of Internal Medicine, Division of Cardiology, University of Texas Health Science Center at Houston, 6431 Fannin, MSB 6.039, Houston, TX 77030, USA.
Pakala
R
R
Katagiri
T
T
Benedict
C R
CR
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000494:pharmacology*; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000494:pharmacology*; D008938:Mitosis / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D011817:Rabbits; D012016:Reference Values; D012680:Sensitivity and Specificity; D012701:Serotonin / Q000494:pharmacology*
D016166:Free Radical Scavengers; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D012701:Serotonin