PMID- 10086975
OWN - NLM
STAT- MEDLINE
DCOM- 19990414
LR  - 20190623
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 99
IP  - 11
DP  - 1999 Mar 23
TI  - Tissue expression and immunolocalization of tumor necrosis factor-alpha in 
      postinfarction dysfunctional myocardium.
PG  - 1492-8
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is markedly elevated in 
      advanced heart failure. It is not known whether tissue TNF-alpha is elevated in 
      the common setting of myocardial infarction leading to heart failure and what the 
      source of TNF-alpha is. To determine this, we studied the expression and protein 
      localization of TNF-alpha and its 2 main receptors (TNF-R1/R2) in a rat model of 
      large infarction. METHODS AND RESULTS: Male rats were randomized to proximal left 
      anterior descending ligation. The animals were killed on days 1, 3, 10, and 35 
      after ligation to examine gene expression and protein production of TNF-alpha and 
      TNF-R1/R2 from the infarct, peri-infarct, and contralateral zones of infarcted 
      heart. There was increased TNF-alpha mRNA production throughout the myocardium at 
      day 1, and detectable expression persisted to day 35 after myocardial infarction. 
      The expression of this cytokine is not confined strictly to the infarct or 
      peri-infarct zones but is expressed by cardiac myocytes within the myocardium in 
      the contralateral normal zone. Changes in gene expression are mirrored initially 
      by augmented protein production within the myocytes. Levels of TNF-alpha protein 
      in the infarct and peri-infarct zones rose early to 8- to 10-fold above normal 
      levels and rose to 4- to 5-fold in the contralateral zone. Finally, expression of 
      the TNF-R1 mRNA transcripts was upregulated at days 3 and 10 after ligation in 
      the infarct and peri-infarct zones, suggesting that the signal transduction 
      pathways necessary for TNF-alpha in the heart remain intact as TNF-alpha 
      biosynthesis increases. CONCLUSIONS: TNF-alpha is present early in a model of 
      large myocardial infarction and is sustained into the later stage within the 
      myocardium. Expression of this cytokine is not only confined strictly to the 
      infarct or peri-infarct zone but is expressed by cardiac myocytes within the 
      myocardium contralateral to the infarct. Therefore TNF-alpha production forms a 
      part of an important intrinsic myocardial stress response system to injury.
FAU - Irwin, M W
AU  - Irwin MW
AD  - Centre for Cardiovascular Research, The Toronto Hospital, Amgen Institute, 
      Ontario Cancer Institute, Ontario, Canada.
FAU - Mak, S
AU  - Mak S
FAU - Mann, D L
AU  - Mann DL
FAU - Qu, R
AU  - Qu R
FAU - Penninger, J M
AU  - Penninger JM
FAU - Yan, A
AU  - Yan A
FAU - Dawood, F
AU  - Dawood F
FAU - Wen, W H
AU  - Wen WH
FAU - Shou, Z
AU  - Shou Z
FAU - Liu, P
AU  - Liu P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Antigens, CD)
RN  - 0 (Muscle Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Antigens, CD/biosynthesis/genetics
MH  - Blotting, Northern
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression Regulation
MH  - Heart Failure/etiology/*metabolism/pathology
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization
MH  - Male
MH  - Muscle Proteins/*biosynthesis/genetics
MH  - Myocardial Infarction/complications/*metabolism/pathology
MH  - Myocardium/*metabolism/pathology
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Tumor Necrosis Factor/biosynthesis/genetics
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Receptors, Tumor Necrosis Factor, Type II
MH  - Tumor Necrosis Factor-alpha/analysis/*biosynthesis/genetics
EDAT- 1999/03/23 00:00
MHDA- 1999/03/23 00:01
CRDT- 1999/03/23 00:00
PHST- 1999/03/23 00:00 [pubmed]
PHST- 1999/03/23 00:01 [medline]
PHST- 1999/03/23 00:00 [entrez]
AID - 10.1161/01.cir.99.11.1492 [doi]
PST - ppublish
SO  - Circulation. 1999 Mar 23;99(11):1492-8. doi: 10.1161/01.cir.99.11.1492.