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Induction of cyclooxygenase-2 in rat vascular smooth muscle cells in vitro and in vivo. J Biol Chem 1994 Mar 18;269(11):8504-9

Date

03/18/1994

Pubmed ID

8132578

Scopus ID

2-s2.0-0028366113   139 Citations

Abstract

Prostaglandins are synthesized from arachidonic acid by the rate-limiting enzyme cyclooxygenase (prostaglandin G/H synthase). Active cyclooxygenase is encoded by two distinct and independently regulated genes, termed cyclooxygenase-1 (cox1) and cyclooxygenase-2 (cox2). In this investigation, we examined the expression of cox1 and cox2 mRNA in rat aorta following balloon deendothelialization (BDE) in vivo and in rat aortic smooth muscle cells (SMC) after serum stimulation in vitro. Two h after BDE, rat aortic cox2 mRNA levels increased greater than 50-fold relative to the lowest detectable levels on days 2 and 14. No message was detectable in non-BDE control rat aortas. Similar to the results found in vivo, cultured SMC exhibited a greater than 45-fold increase in cox2 mRNA levels after a 2-h exposure to serum. This increase was transient because cox2 levels declined at 4 and 8 h. In contrast, minimal changes in cox1 mRNA levels were observed after BDE or serum treatments. Increased levels of cox2 mRNA and corresponding protein synthesis led to an accumulation of total cyclooxygenase protein, which remained elevated 24 h after serum stimulation. Serum-treated SMC also generated greater amounts of cyclooxygenase-dependent metabolites than quiescent SMC as evidenced by marked increases in prostaglandin E2 content in conditioned media. This increase is associated with a 2.5-3.0-fold increased rate of arachidonic acid conversion to prostaglandin E2. Our data indicate that injury and serum stimulation differentially regulate mRNA and protein expression of two distinct cox genes in vascular SMC in vivo and in vitro. The findings suggest that the prostanoid responses after vascular injury are, in part, mediated by acute increases in cox2 mRNA and cyclooxygenase-2 protein.

Author List

Pritchard KA Jr, O'Banion MK, Miano JM, Vlasic N, Bhatia UG, Young DA, Stemerman MB

Author

Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Aorta
Blotting, Northern
Blotting, Western
Cells, Cultured
Culture Media
Culture Media, Serum-Free
Endothelium, Vascular
Enzyme Induction
Gene Expression Regulation, Enzymologic
Isoenzymes
Male
Multigene Family
Muscle, Smooth, Vascular
Prostaglandin-Endoperoxide Synthases
RNA, Messenger
Rats
Rats, Sprague-Dawley
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a