PMID- 11668085
OWN - NLM
STAT- MEDLINE
DCOM- 20011205
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 281
IP  - 5
DP  - 2001 Nov
TI  - DNA enzyme targeting TNF-alpha mRNA improves hemodynamic performance in rats with 
      postinfarction heart failure.
PG  - H2211-7
AB  - Tumor necrosis factor-alpha (TNF-alpha) probably affects the pathogenesis of 
      heart failure. Here we have investigated the therapeutic potential of a 
      nuclease-resistant DNA enzyme that specifically cleaves TNF-alpha mRNA. A 
      phosphorothioate-modified DNA enzyme was designed to retain similar cleavage 
      activity as its unmodified version, and that inhibited the expression of 
      TNF-alpha in vitro. To test its efficacy in vivo, postinfarction congestive heart 
      failure was induced in anesthetized rats by ligation of the left coronary artery. 
      A 4-wk treatment with the DNA enzyme induced a substantial reduction in left 
      ventricular end-diastolic pressure and lung weight concomitant with an increase 
      in arterial blood pressure and myocardial blood flow compared with controls. The 
      concentration of TNF-alpha in coronary sinus blood was markedly lowered on 
      treatment, and myocardial TNF-alpha mRNA was substantially reduced. Recovery 
      studies showed that the DNA enzyme cleavage activity was present within the 
      myocardium throughout the observation period and had no apparent toxic effects. 
      Our findings indicate that DNA enzyme-based therapy may hold promise in the 
      treatment of this debilitating disease.
FAU - Iversen, P O
AU  - Iversen PO
AD  - Institute for Nutrition Research, University of Oslo, 0316 Oslo, Norway. 
      poiversen@hotmail.com
FAU - Nicolaysen, G
AU  - Nicolaysen G
FAU - Sioud, M
AU  - Sioud M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Enzymes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Enzymes/chemical synthesis/*pharmacology
MH  - Heart Failure/*drug therapy/physiopathology
MH  - Hemodynamics
MH  - Male
MH  - Myocardial Infarction/*drug therapy/physiopathology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 2001/10/23 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/23 10:00
PHST- 2001/10/23 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/23 10:00 [entrez]
AID - 10.1152/ajpheart.2001.281.5.H2211 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2001 Nov;281(5):H2211-7. doi: 
      10.1152/ajpheart.2001.281.5.H2211.