PMID- 9577949
OWN - NLM
STAT- MEDLINE
DCOM- 19980527
LR  - 20190623
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 97
IP  - 14
DP  - 1998 Apr 14
TI  - Cardiac failure in transgenic mice with myocardial expression of tumor necrosis 
      factor-alpha.
PG  - 1375-81
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine 
      that has been detected in several human cardiac-related conditions, including 
      congestive heart failure and septic cardiomyopathy. In these conditions, the 
      origin of TNF-alpha secretion is, at least in part, cardiac myocytes. METHODS AND 
      RESULTS: To determine the consequences of TNF-alpha production by cardiac 
      myocytes in vivo, we developed transgenic mice in which expression of a murine 
      TNF-alpha coding sequence was driven by the murine alpha-myosin heavy chain 
      promoter. Four transgenic founders developed an identical illness consisting of 
      tachypnea, decreased activity, and hunched posture. In vivo, ECG-gated MRI of 
      symptomatic transgenic mice documented a severe impairment of cardiac function 
      evidenced by biventricular dilatation and depressed ejection fractions. All 
      transgenic mice died prematurely. Pathological examination of affected animals 
      revealed a globular dilated heart, bilateral pleural effusions, myocyte 
      apoptosis, and transmural myocarditis in both the right and left ventricular free 
      walls, septum, and atrial chambers. In all terminally ill animals, there was 
      significant biventricular fibrosis and atrial thrombosis. CONCLUSIONS: This is 
      the first report detailing the effects of tissue-specific production of TNF-alpha 
      by cardiac myocytes in vivo. These findings indicate that production of TNF-alpha 
      by cardiac myocytes is sufficient to cause severe cardiac disease and support a 
      causal role for this cytokine in the pathogenesis of human cardiac disease.
FAU - Bryant, D
AU  - Bryant D
AD  - Department of Pediatrics, The University of Texas Southwestern Medical Center, 
      Dallas 75235-9063, USA.
FAU - Becker, L
AU  - Becker L
FAU - Richardson, J
AU  - Richardson J
FAU - Shelton, J
AU  - Shelton J
FAU - Franco, F
AU  - Franco F
FAU - Peshock, R
AU  - Peshock R
FAU - Thompson, M
AU  - Thompson M
FAU - Giroir, B
AU  - Giroir B
LA  - eng
GR  - N01-HD-5-3229/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
CIN - Circulation. 1998 Apr 14;97(14):1340-1. PMID: 9577943
MH  - Animals
MH  - Cardiomyopathies/*metabolism
MH  - Disease Models, Animal
MH  - Electrocardiography
MH  - Heart Failure/genetics/*metabolism
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Mice
MH  - Mice, Transgenic
MH  - Myocardium/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 1998/05/13 00:00
MHDA- 1998/05/13 00:01
CRDT- 1998/05/13 00:00
PHST- 1998/05/13 00:00 [pubmed]
PHST- 1998/05/13 00:01 [medline]
PHST- 1998/05/13 00:00 [entrez]
AID - 10.1161/01.cir.97.14.1375 [doi]
PST - ppublish
SO  - Circulation. 1998 Apr 14;97(14):1375-81. doi: 10.1161/01.cir.97.14.1375.