PMID- 12480812
OWN - NLM
STAT- MEDLINE
DCOM- 20021220
LR  - 20220318
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 91
IP  - 12
DP  - 2002 Dec 13
TI  - Tumor necrosis factor-alpha-induced AT1 receptor upregulation enhances 
      angiotensin II-mediated cardiac fibroblast responses that favor fibrosis.
PG  - 1119-26
AB  - Extracellular matrix (ECM) remodeling after myocardial infarction (MI) is an 
      important determinant of cardiac function. Tumor necrosis factor-alpha 
      (TNF-alpha) and angiotensin (Ang) II levels increase after MI and both factors 
      affect fibroblast functions. The type 1 (AT1) receptor that mediates most Ang II 
      effects is upregulated after MI in cardiac fibroblasts, and there is evidence 
      that this is caused by TNF-alpha. We sought to determine if TNF-alpha-induced AT1 
      receptor upregulation alters fibroblast responsiveness to Ang II and if this 
      effect differs from direct TNF-alpha effects on fibroblast functions. In cultured 
      neonatal rat cardiac fibroblasts, TNF-alpha reduced cellular [3H]-proline 
      incorporation, increased matrix metalloproteinase-2 (MMP-2) activity and protein, 
      and increased TIMP-1 protein levels. In cardiac fibroblasts with 
      TNF-alpha-induced AT1 receptor upregulation, Ang II-stimulated [3H]proline 
      incorporation and TIMP-1 protein production was approximately 2-fold greater than 
      in nonpretreated fibroblasts. Angiotensin II reduced MMP-2 activity and protein 
      level only in TNF-alpha-pretreated fibroblasts. Angiotensin II effects were 
      inhibited by selective AT1 (but not AT2) receptor blockers. Thus, 
      TNF-alpha-induced AT1 receptor upregulation enhances Ang II-mediated functions 
      that favor fibrosis. These effects are mostly directionally opposite of direct 
      TNF-alpha effects on cardiac fibroblasts. Recognition of multifaceted TNF-alpha 
      effects provides new insights into post-MI ECM remodeling.
FAU - Peng, JianFeng
AU  - Peng J
AD  - Department of Medicine, Division of Cardiology, University of California, San 
      Diego, Calif, USA.
FAU - Gurantz, Devorah
AU  - Gurantz D
FAU - Tran, Van
AU  - Tran V
FAU - Cowling, Randy T
AU  - Cowling RT
FAU - Greenberg, Barry H
AU  - Greenberg BH
LA  - eng
GR  - R01 HL63909/HL/NHLBI NIH 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 (Angiotensin Receptor Antagonists)
RN  - 0 (Imidazoles)
RN  - 0 (Pyridines)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (Receptors, Angiotensin)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11128-99-7 (Angiotensin II)
RN  - 130663-39-7 (PD 123319)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Angiotensin II/*metabolism/pharmacology
MH  - Angiotensin Receptor Antagonists
MH  - Animals
MH  - Animals, Newborn
MH  - Cardiomyopathies/physiopathology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Extracellular Matrix/metabolism
MH  - Fibroblasts/cytology/*drug effects/metabolism
MH  - Fibrosis/etiology/physiopathology
MH  - Imidazoles/pharmacology
MH  - Losartan/pharmacology
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Proline/metabolism/pharmacokinetics
MH  - Pyridines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Angiotensin, Type 1
MH  - Receptor, Angiotensin, Type 2
MH  - Receptors, Angiotensin/*metabolism
MH  - Tissue Inhibitor of Metalloproteinase-1/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Up-Regulation/*drug effects
EDAT- 2002/12/14 04:00
MHDA- 2002/12/21 04:00
CRDT- 2002/12/14 04:00
PHST- 2002/12/14 04:00 [pubmed]
PHST- 2002/12/21 04:00 [medline]
PHST- 2002/12/14 04:00 [entrez]
AID - 10.1161/01.res.0000047090.08299.d5 [doi]
PST - ppublish
SO  - Circ Res. 2002 Dec 13;91(12):1119-26. doi: 10.1161/01.res.0000047090.08299.d5.