PMID- 10436170
OWN - NLM
STAT- MEDLINE
DCOM- 19990902
LR  - 20190706
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 85
IP  - 3
DP  - 1999 Aug 6
TI  - Tumor necrosis factor-alpha upregulates angiotensin II type 1 receptors on 
      cardiac fibroblasts.
PG  - 272-9
AB  - Angiotensin II (Ang II) plays an important role in post-myocardial infarction 
      (MI) remodeling. Most Ang II effects related to remodeling involve activation of 
      the type 1 receptor (AT(1)). Although the AT(1) receptor is upregulated on 
      cardiac fibroblasts post-MI, little is known about the mechanisms involved in the 
      process. Consequently, we tested whether growth factors known to be present in 
      the remodeling heart increased AT(1) mRNA levels. Using quantitative competitive 
      reverse transcription-polymerase chain reaction, we found that norepinephrine, 
      endothelin, atrial natriuretic peptide, and bradykinin had no significant effect 
      on AT(1) mRNA levels. Ang II, transforming growth factor-beta(1), and basic 
      fibroblast growth factor reduced AT(1) mRNA levels (P<0.02). Tumor necrosis 
      factor-alpha (TNF-alpha), however, produced a marked increase in AT(1) mRNA. 
      After 24 hours of TNF-alpha incubation, AT(1) mRNA increased by 5-fold above 
      control levels (P<0.01). The EC(50) for the TNF-alpha effect was 4.6 ng/mL (0.2 
      nmol/L). Interleukin (IL)-1beta caused a 2.4-fold increase, whereas IL-2 and IL-6 
      had no significant effect. Studies of TNF-alpha enhancement of AT(1) mRNA levels 
      demonstrate that the increase was not due to a change in transcript stability. 
      TNF-alpha treatment for 48 hours also resulted in a 3-fold increase in AT(1) 
      surface receptor and a 2-fold increase in Ang II-induced production of inositol 
      phosphates. The present findings provide evidence for TNF-alpha regulation of 
      AT(1) receptor density on cardiac fibroblasts. Because TNF-alpha concentration 
      and AT(1) receptor density increase in the myocardium after MI, these results 
      raise the possibility that TNF-alpha modulates post-MI remodeling by enhancing 
      Ang II effects on cardiac fibroblasts.
FAU - Gurantz, D
AU  - Gurantz D
AD  - Department of Medicine, Division of Cardiology, University of California, San 
      Diego Medical Center, San Diego, CA, USA.
FAU - Cowling, R T
AU  - Cowling RT
FAU - Villarreal, F J
AU  - Villarreal FJ
FAU - Greenberg, B H
AU  - Greenberg BH
LA  - eng
GR  - NL-03160/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Inositol Phosphates)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (Receptors, Angiotensin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Drug Stability
MH  - Fibroblasts/drug effects/*metabolism
MH  - Inositol Phosphates/biosynthesis
MH  - Myocardium/cytology/*metabolism
MH  - RNA, Messenger/chemistry/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Angiotensin, Type 1
MH  - Receptor, Angiotensin, Type 2
MH  - Receptors, Angiotensin/drug effects/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Up-Regulation/physiology
EDAT- 1999/08/07 00:00
MHDA- 1999/08/07 00:01
CRDT- 1999/08/07 00:00
PHST- 1999/08/07 00:00 [pubmed]
PHST- 1999/08/07 00:01 [medline]
PHST- 1999/08/07 00:00 [entrez]
AID - 10.1161/01.res.85.3.272 [doi]
PST - ppublish
SO  - Circ Res. 1999 Aug 6;85(3):272-9. doi: 10.1161/01.res.85.3.272.