Nicotine regulates basic fibroblastic growth factor and transforming growth factor beta1 production in endothelial cells.
Nicotine, a constituent of cigarette smoking, may induce atherosclerosis through the production of growth factors. The pattern of bFGF and TGF beta1 production and release by bovine aortic endothelial cells (EC) stimulated with nicotine (from 6 x 10(-4) to 6 x 10(-8) M) was studied. EC viability and count were assessed. The presence of bFGF and TGF beta1 in serum-free conditioned media was determined by the inhibition antibody-binding assay and Western blot analysis. Mitogenic activity of nicotine on EC was also determined. Polymerase chain reaction (PCR) was used to study the expression of bFGF and TGF beta1. The bFGF release after nicotine stimulation was greater than controls, whereas TGF beta1 release was lower. At a nicotine concentration of 6 x 10(-6) M we noted the greatest mitogenic activity. The addition of monoclonal antibody anti-bFGF decreased the tritiated thymidine uptake of EC exposed to nicotine but the addition of monoclonal antibody anti-TGF beta1 had no significant effect. bFGF mRNA expression was significantly higher in EC exposed to nicotine than in controls, whereas TGF beta1 mRNA expression was not modified. From these data we concluded that nicotine regulates bFGF production and release and TGF beta1 release and may have a key role in the development and progression of atherosclerosis.
Cucina
A
A
1st Department of Surgery, University of Rome "La Sapienza,", Rome, Italy. acucina@uniroma1.it
Corvino
V
V
Sapienza
P
P
Borrelli
V
V
Lucarelli
M
M
Scarpa
S
S
Strom
R
R
Santoro-D'Angelo
L
L
Cavallaro
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001011:Aorta; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D015153:Blotting, Western; D002417:Cattle; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008934:Mitogens / Q000378:metabolism / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology* / Q000633:toxicity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D008934:Mitogens; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D009538:Nicotine; D004247:DNA