Document Detail


Lysophosphatidylcholine and reactive oxygen species mediate the synergistic effect of mildly oxidized LDL with serotonin on vascular smooth muscle cell proliferation.
MedLine Citation:
PMID:  11245650     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Mild oxidation of LDL enhances its atherogenic potential and induces a synergistic interaction with serotonin (5HT) on vascular smooth muscle cell (VSMC) proliferation. Because of its complex chemical nature, the mitogenic components of mildly oxidized LDL (moxLDL) remain unclear. METHODS AND RESULTS: We examined both the effects of lysophosphatidylcholine (LPC) and hydrogen peroxide (H(2)O(2)), a donor of reactive oxygen species, as major components of moxLDL and their interactions with 5HT on VSMC proliferation. Growth-arrested VSMCs were incubated with different concentrations of moxLDL, LPC, H(2)O(2), or LPC with H(2)O(2) in the absence or presence of 5HT. DNA synthesis in VSMCs was examined by [(3)H]thymidine incorporation. MoxLDL, LPC, H(2)O(2), and 5HT stimulated DNA synthesis in a dose-dependent manner. MoxLDL had a maximal stimulatory effect at a concentration of 5 microg/mL (211%), LPC at 15 micromol/L (156%), H(2)O(2) at 5 micromol/L (179%), and 5HT at 50 micromol/L (205%). Added together, moxLDL (50 ng/mL) and 5HT (50 micromol/L) synergistically increased DNA synthesis (443%). Coincubation of LPC (1 micromol/L) with H(2)O(2) (0.5 micromol/L) and 5HT (5 micromol/L) resulted in a synergistic increase in DNA synthesis (439%), which was nearly equal to that of moxLDL with 5HT (443%). The combined effects of LPC, H(2)O(2), and 5HT on DNA synthesis were completely reversed by the combined use of an antioxidant, N:-acetylcysteine (400 micromol/L) or butylated hydroxytoluene (20 micromol/L), with a 5HT(2) receptor antagonist, LY281067 (10 microg/mL). CONCLUSIONS: Our results suggest that both LPC and reactive oxygen species may contribute to the mitogenic effect of moxLDL on VSMCs and its synergistic effect with 5HT.
Authors:
T Watanabe; R Pakala; S Koba; T Katagiri; C R Benedict
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  103     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-03-14     Completed Date:  2001-05-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1440-5     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Division of Cardiology, University of Texas-Houston Health Science Center, Houston, TX 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology
Cell Count
Cell Division / drug effects
DNA / biosynthesis,  drug effects
Drug Synergism
Humans
Hydrogen Peroxide / pharmacology*
Lipoproteins, LDL / pharmacology*
Lysergic Acid / analogs & derivatives*,  pharmacology
Lysophosphatidylcholines / pharmacology*
Male
Muscle, Smooth, Vascular / cytology,  drug effects*,  physiology
Rabbits
Reactive Oxygen Species / metabolism
Serotonin / pharmacology*
Serotonin Antagonists / pharmacology
Grant Support
ID/Acronym/Agency:
R01-HL-39916/HL/NHLBI NIH HHS; R01-HL-50653/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Lipoproteins, LDL; 0/Lysophosphatidylcholines; 0/Reactive Oxygen Species; 0/Serotonin Antagonists; 0/oxidized low density lipoprotein; 108674-87-9/sergolexole; 50-67-9/Serotonin; 7722-84-1/Hydrogen Peroxide; 82-58-6/Lysergic Acid; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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