PMID- 10385500
OWN - NLM
STAT- MEDLINE
DCOM- 19990716
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 99
IP  - 25
DP  - 1999 Jun 29
TI  - Tumor necrosis factor-alpha-converting enzyme and tumor necrosis factor-alpha in 
      human dilated cardiomyopathy.
PG  - 3260-5
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the 
      pathogenesis of dilated cardiomyopathy (DCM). TNF-alpha-converting enzyme (TACE) 
      has recently been purified and its complementary DNA cloned. The expression of 
      TACE results in the production of a functional enzyme that has precursor 
      TNF-alpha in the mature form. The aim of this study was to determine whether TACE 
      is expressed with TNF-alpha in myocardium and whether levels of TACE and 
      TNF-alpha are related to clinical severity of DCM. METHODS AND RESULTS: 
      Endomyocardial tissues were obtained from 30 patients with DCM and 5 control 
      subjects. TNF-alpha and TACE mRNA levels were measured by a novel real-time 
      quantitative reverse transcriptase-polymerase chain reaction method. Expression 
      of TNF-alpha and TACE proteins was determined by immunohistochemical analysis. 
      TNF-alpha mRNA was expressed in DCM patients (TNF-alpha/GAPDH ratio 0.85+/-0.24) 
      but not in control subjects. TACE mRNA expression was significantly greater in 
      DCM patients than in control subjects (TACE/GAPDH ratio 2.52+/-0.59 vs 
      0.03+/-0.02, P<0.05). A positive correlation was found between TNF-alpha and TACE 
      mRNA levels (r=0.779, P<0.001). TACE and TNF-alpha immunostaining was observed in 
      myocytes in patients with DCM. When 2 subgroups of DCM were divided on the basis 
      of left ventricular end-systolic diameter (LVESD) of 45 mm and left ventricular 
      ejection fraction (LVEF) of 40%, the DCM subgroup with high LVESD (>/=45 mm) 
      showed significantly greater expression of TACE (P=0.02) and TNF-alpha (P=0. 001) 
      than did the low LVESD subgroup (<45 mm). In addition, the DCM subgroup with 
      lower LVEF (<40%) showed higher expression of TACE (P=0.006) and TNF-alpha 
      (P=0.01) than did the subgroup with high LVEF (>/=40%). CONCLUSIONS: This study 
      has shown that increased myocardial TACE expression is associated with elevated 
      myocardial TNF-alpha expression in both mRNA and protein levels in clinically 
      advanced DCM.
FAU - Satoh, M
AU  - Satoh M
AD  - Second Department of Internal Medicine, Iwate Medical University School of 
      Medicine, Iwate, Japan. staohm@iwate-med.ac.jp
FAU - Nakamura, M
AU  - Nakamura M
FAU - Saitoh, H
AU  - Saitoh H
FAU - Satoh, H
AU  - Satoh H
FAU - Maesawa, C
AU  - Maesawa C
FAU - Segawa, I
AU  - Segawa I
FAU - Tashiro, A
AU  - Tashiro A
FAU - Hiramori, K
AU  - Hiramori K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (DNA Primers)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
SB  - IM
MH  - ADAM Proteins
MH  - ADAM17 Protein
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Cardiomyopathy, Dilated/*blood/enzymology
MH  - DNA Primers
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Metalloendopeptidases/*blood/genetics
MH  - Middle Aged
MH  - RNA, Messenger/analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Severity of Illness Index
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
EDAT- 1999/06/29 00:00
MHDA- 1999/06/29 00:01
CRDT- 1999/06/29 00:00
PHST- 1999/06/29 00:00 [pubmed]
PHST- 1999/06/29 00:01 [medline]
PHST- 1999/06/29 00:00 [entrez]
AID - 10.1161/01.cir.99.25.3260 [doi]
PST - ppublish
SO  - Circulation. 1999 Jun 29;99(25):3260-5. doi: 10.1161/01.cir.99.25.3260.