Angiotensin II and endothelin-1 increase fibroblast growth factor-2 mRNA expression in vascular smooth muscle cells.
The vasoactive hormone angiotensin II (Ang II) can stimulate vascular smooth muscle cell (SMC) hypertrophy and proliferation; thus, it may have an important role in the pathogenesis of hypertension, atherosclerosis and restenosis. Several studies have indicated that Ang II bioactivity on SMC may depend, at least in part, on its ability to induce the expression of polypeptide growth factors that can function in an autocrine manner. Here we report that Ang II treatment of rat aortic SMC increases fibroblast growth factor-2 (FGF-2) but not FGF-1 mRNA levels. Increased FGF-2 mRNA expression is first detectable at 30 min after Ang II addition and maximal levels are present at 8 hr. Ang II induction of FGF-2 mRNA levels is dependent on de novo RNA and protein synthesis. The Ang II effect can be blocked by treatment with either the Ang II type 1 receptor-selective antagonist CI-996 or the tyrosine kinase inhibitor genistein. The potent vasoconstrictor and SMC mitogen endothelin-1 can also induce FGF-2 mRNA levels in rat aortic SMC. These results indicate that FGF-2 gene expression is up-regulated by two distinct vasoactive peptides implicated in vascular SMC growth control in vivo.
Peifley
K A
KA
Department of Vascular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.
Winkles
J A
JA
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry; D016895:Culture Media, Serum-Free; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011921:Rats, Inbred WKY
D057911:Angiotensin Receptor Antagonists; D016895:Culture Media, Serum-Free; D019332:Endothelin-1; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D000804:Angiotensin II; D003609:Dactinomycin; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C