PMID- 10785514
OWN - NLM
STAT- MEDLINE
DCOM- 20000530
LR  - 20190706
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 86
IP  - 8
DP  - 2000 Apr 28
TI  - Cyclooxygenase-2 is required for tumor necrosis factor-alpha- and angiotensin 
      II-mediated proliferation of vascular smooth muscle cells.
PG  - 906-14
AB  - Tumor necrosis factor-alpha (TNF-alpha) and angiotensin II (Ang II) induced a 
      transient increase in vascular smooth muscle cell (VSMC) cyclooxygenase-2 (COX-2) 
      mRNA accumulation, without affecting COX-1 mRNA levels. The kinetics of COX-2 
      mRNA accumulation were similar in VSMCs challenged with either TNF-alpha or Ang 
      II; mRNA accumulation peaked at 2 hours and decreased to control levels by 
      approximately 6 hours. Accumulation of COX-2 mRNA was associated with a 
      time-dependent increase of COX-2 protein expression that displayed similar 
      kinetics in response to either TNF-alpha or Ang II. Both the increase in COX-2 
      mRNA accumulation and protein expression in response to either TNF-alpha or Ang 
      II were inhibited by the mitogen-activated protein/extracellular signal-regulated 
      kinase (MEK) inhibitor PD098059. In addition, the AT(1)-selective receptor 
      antagonist losartan attenuated the Ang II-mediated increase in COX-2 mRNA 
      accumulation; the AT(2)-selective antagonist PD123319 had no effect. Prostacyclin 
      I(2) synthesis was tightly coupled to expression of COX-2, whereas prostaglandin 
      E(2) and thromboxane A(2) (TXA(2)) synthesis may be associated with differential 
      usage of COX-1 and COX-2. The COX-2-selective inhibitors NS-398 and nimesulide 
      and the TXA(2) receptor antagonist BMS 180,291 inhibited TNF-alpha- and Ang 
      II-mediated increases in DNA content and cell number by approximately 95%. These 
      findings suggest that a prostanoid derived from COX-2, possibly TXA(2), may 
      contribute to VSMC hyperplasia in vessel injury or pathophysiological conditions 
      associated with elevated levels of either TNF-alpha or Ang II.
FAU - Young, W
AU  - Young W
AD  - Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
FAU - Mahboubi, K
AU  - Mahboubi K
FAU - Haider, A
AU  - Haider A
FAU - Li, I
AU  - Li I
FAU - Ferreri, N R
AU  - Ferreri NR
LA  - eng
GR  - R01HL56423/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Isoenzymes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vasoconstrictor Agents)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
SB  - IM
MH  - Angiotensin II/*pharmacology
MH  - Animals
MH  - Cell Division/drug effects/physiology
MH  - Cells, Cultured
MH  - Cyclooxygenase 2
MH  - Isoenzymes/*physiology
MH  - Male
MH  - Muscle, Smooth, Vascular/*cytology/*physiology
MH  - Prostaglandin-Endoperoxide Synthases/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Vasoconstrictor Agents/*pharmacology
EDAT- 2000/04/29 09:00
MHDA- 2000/06/03 09:00
CRDT- 2000/04/29 09:00
PHST- 2000/04/29 09:00 [pubmed]
PHST- 2000/06/03 09:00 [medline]
PHST- 2000/04/29 09:00 [entrez]
AID - 10.1161/01.res.86.8.906 [doi]
PST - ppublish
SO  - Circ Res. 2000 Apr 28;86(8):906-14. doi: 10.1161/01.res.86.8.906.