PMID- 11994255
OWN - NLM
STAT- MEDLINE
DCOM- 20020613
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 105
IP  - 18
DP  - 2002 May 7
TI  - Angiotensin II induces tumor necrosis factor biosynthesis in the adult mammalian 
      heart through a protein kinase C-dependent pathway.
PG  - 2198-205
AB  - BACKGROUND: Previous studies suggest that angiotensin II (Ang II) upregulates the 
      expression of tumor necrosis factor (TNF) in nonmyocyte cell types; however, the 
      effect of Ang II on TNF expression in the adult mammalian heart is not known. 
      METHODS AND RESULTS: To determine whether Ang II was sufficient to provoke TNF 
      biosynthesis in the adult heart, we examined the effects of Ang II in isolated 
      buffer-perfused Langendorff feline hearts. Ang II (10(-7) mol/L) treatment 
      resulted in a time- and dose-dependent increase in myocardial TNF mRNA and 
      protein biosynthesis in the heart as well as in cultured adult cardiac myocytes. 
      The effects of Ang II on myocardial TNF mRNA and protein synthesis were mediated 
      through the angiotensin type 1 receptor (AT1R), insofar as an AT1R antagonist 
      (AT1a) blocked the effects of Ang II, whereas an angiotensin type 2 receptor 
      (AT2R) antagonist (AT2a) had no effect. Stimulation with Ang II led to the 
      activation of nuclear factor-kappaB and activator protein-1 (AP-1), two 
      transcription factors that are important for TNF gene expression. Nuclear 
      factor-kappaB activation was accompanied by phosphorylation of IkappaBalpha on 
      serine 32 as well as degradation of IkappaBalpha, suggesting that the effects of 
      Ang II were mediated through an IkappaBalpha-dependent pathway. The important 
      role of protein kinase C (PKC) was suggested by studies in which a phorbol ester 
      triggered TNF biosynthesis, and a PKC inhibitor abrogated Ang II-induced TNF 
      biosynthesis. CONCLUSIONS: These studies suggest that Ang II provokes TNF 
      biosynthesis in the adult mammalian heart through a PKC-dependent pathway.
FAU - Kalra, Dinesh
AU  - Kalra D
AD  - Winters Center for Heart Failure Research, Cardiology Section, Department of 
      Medicine, Veterans Administration Medical Center, and Baylor College of Medicine, 
      Houston, Tex 77030, USA.
FAU - Sivasubramanian, Natarajan
AU  - Sivasubramanian N
FAU - Mann, Douglas L
AU  - Mann DL
LA  - eng
GR  - HL-42250-10/10/HL/NHLBI NIH HHS/United States
GR  - P50 HL-O6H/HL/NHLBI NIH HHS/United States
GR  - R01-HL58081-01/HL/NHLBI NIH HHS/United States
GR  - R01-HL61543-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Diglycerides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Angiotensin II/*pharmacology
MH  - Animals
MH  - Cats
MH  - Cells, Cultured
MH  - Diglycerides/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Heart/drug effects
MH  - Kinetics
MH  - Myocardium/cytology/enzymology/*metabolism
MH  - NF-kappa B/metabolism
MH  - Organ Culture Techniques
MH  - Protein Kinase C/antagonists & inhibitors/*physiology
MH  - RNA, Messenger/biosynthesis
MH  - *Signal Transduction
MH  - Transcriptional Activation
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/genetics
EDAT- 2002/05/08 10:00
MHDA- 2002/06/14 10:01
CRDT- 2002/05/08 10:00
PHST- 2002/05/08 10:00 [pubmed]
PHST- 2002/06/14 10:01 [medline]
PHST- 2002/05/08 10:00 [entrez]
AID - 10.1161/01.cir.0000015603.84788.47 [doi]
PST - ppublish
SO  - Circulation. 2002 May 7;105(18):2198-205. doi: 
      10.1161/01.cir.0000015603.84788.47.