title: Ethanol inhibits fibroblast growth factor-induced proliferation of aortic smooth muscle cells.
abstract: OBJECTIVE
  Epidemiological studies have demonstrated that moderate alcohol consumption reduces mortality associated with coronary artery disease. The protective effect is correlated with the amount of ethanol consumed but is unrelated to the form of alcoholic beverage. Adoption of a favorable lipoprotein profile accounts for about half of the protective action of alcohol, but the remaining causative factors remain conjectural. Fibroblast growth factors (FGFs) play important roles in mediating smooth muscle cell (SMC) proliferation and migration, which are key factors in the atherosclerotic process. In the present study, we examined the effect of ethanol on FGF-mediated SMC growth and signaling.
  
  
  RESULTS
  Pharmacologically relevant concentrations of ethanol inhibited the proliferation of a rat aortic SMC line (SV40LT-SMCs) in response to FGF1 and FGF2. Human aortic SMC growth was similarly inhibited by ethanol. Transition into the G2/M phase was specifically affected. FGF-mediated phosphorylation of p42/p44 mitogen-activated protein kinase (MAPK) c-Raf, MAP kinase kinase kinase, MEK1/2 MAP kinase, kinase, stress-activated protein kinase/c-Jun-NH2-terminal kinase, and p38 MAPK were variably reduced by ethanol. The inhibition of intracellular signaling by ethanol was correlated with inhibition of FGF receptor autophosphorylation. By contrast, neither epidermal growth factor receptor autophosphorylation nor epidermal growth factor-mediated p42/p44 MAPK activation was affected by ethanol.
  
  
  CONCLUSIONS
  The findings identify the FGF receptor as an inhibitory target for ethanol, which could account in part for the inhibitory actions of ethanol on SMC proliferation observed in vivo.
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. giancarlo.ghiselli@mail.tju.edu
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Ghiselli
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Mohamad
authors.initials: M
authors.lastname: Kaou
authors.forename: Hazam
authors.initials: H
authors.lastname: Hallak
authors.forename: Raphael
authors.initials: R
authors.lastname: Rubin
mesh_terms: D000818:Animals; D001011:Aorta; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015536:Down-Regulation; D000431:Ethanol / Q000494:pharmacology*; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D000431:Ethanol; C496353:FGFR2 protein, human; C496356:Fgfr2 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases