PMID- 18192036
OWN - NLM
STAT- MEDLINE
DCOM- 20080729
LR  - 20171116
IS  - 1874-1754 (Electronic)
IS  - 0167-5273 (Linking)
VI  - 126
IP  - 3
DP  - 2008 Jun 6
TI  - Imidaprilat inhibits matrix metalloproteinase-2 activity in human cardiac 
      fibroblasts induced by interleukin-1beta via NO-dependent pathway.
PG  - 414-20
LID - 10.1016/j.ijcard.2007.08.134 [doi]
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are widely used in 
      treatment of heart failure, but little is known regarding whether ACE inhibitors 
      regulate the activity of matrix metalloproteinases (MMPs) and the tissue 
      inhibitor of MMPs (TIMPs) in cardiac cells. The purpose of this study was to 
      determine the ability and possible signal pathway involved of imidaprilat, an ACE 
      inhibitor, to modulate MMP-2 and TIMP-2 in human cardiac fibroblasts in the 
      presence of interleukin (IL)-1beta. METHODS AND RESULTS: Using gelatin zymography 
      and RT-PCR and Griess analysis,we found that IL-1beta increased the MMP-2 
      activity and transcription and nitric oxide(NO) production from supernatant of 
      culture medium. These effects of IL-1beta were inhibited by imidaprilat or the NO 
      synthase inhibitor, L-NMMA. Sodium nitroprusside (SNP), an exogenous NO donor, 
      prevented significantly the effects of imidaprilat on MMP-2 inhibition. 
      Imidaprilat alone didn't affect MMP-2 activity and expression. Neither IL-1beta 
      nor imidaprilat has no effect on TIMP-2 transcription in cardiac fibroblasts. 
      CONCLUSIONS: The current study demonstrates imidaprilat inhibits MMP-2 activity 
      and expression in human cardiac fibroblasts induced by IL-1beta via NO-dependent 
      pathway. These data suggest that the beneficial effect of ACE inhibitors against 
      left cardiac remodeling and heart failure may be due at least in part to 
      regulating MMPs activity and expression by modulation of NO pathway.
FAU - Guo, Xiao-Gang
AU  - Guo XG
AD  - Department of Cardiovascular Science, the First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003 China.
FAU - Uzui, Hiroyasu
AU  - Uzui H
FAU - Mizuguchi, Toshihiro
AU  - Mizuguchi T
FAU - Ueda, Takanori
AU  - Ueda T
FAU - Chen, Jun-zhu
AU  - Chen JZ
FAU - Lee, Jong-Dae
AU  - Lee JD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080114
PL  - Netherlands
TA  - Int J Cardiol
JT  - International journal of cardiology
JID - 8200291
RN  - 0 (Imidazolidines)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 63231-63-0 (RNA)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - WUU07Y30IA (imidaprilat)
SB  - IM
MH  - Analysis of Variance
MH  - Cells, Cultured
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Fibroblasts/drug effects/*metabolism
MH  - Humans
MH  - Imidazolidines/*pharmacology
MH  - Interleukin-1beta/*metabolism/pharmacology
MH  - Matrix Metalloproteinase 2/*metabolism
MH  - *Matrix Metalloproteinase Inhibitors
MH  - Myocytes, Cardiac/drug effects/*metabolism
MH  - Nitric Oxide/*metabolism
MH  - Probability
MH  - RNA/analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Risk Factors
MH  - Sensitivity and Specificity
MH  - Signal Transduction/drug effects/physiology
EDAT- 2008/01/15 09:00
MHDA- 2008/07/30 09:00
CRDT- 2008/01/15 09:00
PHST- 2007/05/26 00:00 [received]
PHST- 2007/08/16 00:00 [revised]
PHST- 2007/08/18 00:00 [accepted]
PHST- 2008/01/15 09:00 [pubmed]
PHST- 2008/07/30 09:00 [medline]
PHST- 2008/01/15 09:00 [entrez]
AID - S0167-5273(07)01930-4 [pii]
AID - 10.1016/j.ijcard.2007.08.134 [doi]
PST - ppublish
SO  - Int J Cardiol. 2008 Jun 6;126(3):414-20. doi: 10.1016/j.ijcard.2007.08.134. Epub 
      2008 Jan 14.