PMID- 12873541
OWN - NLM
STAT- MEDLINE
DCOM- 20040423
LR  - 20231213
IS  - 1053-2498 (Print)
IS  - 1053-2498 (Linking)
VI  - 22
IP  - 7
DP  - 2003 Jul
TI  - Increased expression of extracellular matrix regulators TIMP1 and MMP1 in 
      deteriorating heart failure.
PG  - 738-44
AB  - BACKGROUND: The authors previously identified and compared alterations in gene 
      expression in the myocardia of patients with deteriorating heart failure who 
      underwent left ventricular assist device (LVAD) implantation with those of 
      patients with stable end-stage failure (ESF). We hypothesized that matrix 
      metalloproteinases (MMPs) and their endogenous inhibitors, the tissue inhibitors 
      of MMPs (TIMPs), would be implicated in the mechanisms that underlie 
      deteriorating heart failure. METHODS: Gridded macro-array filters were used to 
      provide a broad overview of MMP and TIMP mRNA expression in heart failure. 
      Precise mRNA levels of TIMP1, MMP1, and beta-spectrin were determined using 
      quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) 
      of myocardial samples from 27 patients with deteriorating heart failure who 
      underwent LVAD implantation, from 17 patients with stable ESF who underwent 
      elective heart transplantation, and from 28 donor organs with good hemodynamic 
      function. RESULTS: Gridded macro-arrays analysis of pooled failing heart samples 
      determined that TIMP1 mRNA was the most readily detectable TIMP in failing 
      myocardium. Quantitative RT-PCR showed that expression levels in individual 
      patients were similar in patients with stable ESF (1.00 +/- 0.24, n = 17) and in 
      donor organ samples (1.49 +/- 0.22, n = 28) but were significantly increased in 
      the deteriorating heart failure group (5.38 +/- 0.32, n = 26, p < 0.0001 compared 
      with patients with ESF). Similarly, MMP1 levels did not differ between donor and 
      ESF groups but increased in the deteriorating failure group (6.04 +/- 0.50, n = 
      27, p < 0.001 compared with the ESF group). Levels of beta-II spectrin were the 
      same in all 3 groups. Both TIMP1 and MMP1 showed positive correlation with each 
      other and with previously determined levels of mRNA for both interleukin-1beta 
      (IL-1beta) and IL-6 in this patient series when considering all patients 
      individually, but neither correlated with tumor necrosis factor alpha. 
      CONCLUSIONS: Patients with deteriorating heart failure have increased expression 
      of TIMP1 and MMP1 mRNA. Correlation with pro-inflammatory cytokines suggests 
      common pathways of regulation and potential activation by IL-6 and IL1-beta.
FAU - Barton, Paul J R
AU  - Barton PJ
AD  - Heart Science Centre, Royal Brompton and Harefield Hospital, Harefield, 
      Middlesex, United Kingdom
FAU - Birks, Emma J
AU  - Birks EJ
FAU - Felkin, Leanne E
AU  - Felkin LE
FAU - Cullen, Martin E
AU  - Cullen ME
FAU - Koban, Maren U
AU  - Koban MU
FAU - Yacoub, Magdi H
AU  - Yacoub MH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-3)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.24.34 (Matrix Metalloproteinase 8)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Adult
MH  - Cytokines/metabolism
MH  - Extracellular Matrix/*metabolism
MH  - Female
MH  - Gene Expression Regulation, Enzymologic/genetics
MH  - Genetic Predisposition to Disease/genetics
MH  - Heart Failure/*metabolism
MH  - Heart Transplantation
MH  - Heart-Assist Devices
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinase 1/*biosynthesis/genetics
MH  - Matrix Metalloproteinase 8/biosynthesis/genetics
MH  - Matrix Metalloproteinase 9/biosynthesis/genetics
MH  - Middle Aged
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Statistics as Topic
MH  - Tissue Inhibitor of Metalloproteinase-1/*biosynthesis/genetics
MH  - Tissue Inhibitor of Metalloproteinase-2/biosynthesis/genetics
MH  - Tissue Inhibitor of Metalloproteinase-3/biosynthesis/genetics
MH  - Tissue Inhibitor of Metalloproteinases/biosynthesis/genetics
MH  - Treatment Outcome
MH  - Tissue Inhibitor of Metalloproteinase-4
EDAT- 2003/07/23 05:00
MHDA- 2004/04/24 05:00
CRDT- 2003/07/23 05:00
PHST- 2003/07/23 05:00 [pubmed]
PHST- 2004/04/24 05:00 [medline]
PHST- 2003/07/23 05:00 [entrez]
AID - S1053249802005570 [pii]
AID - 10.1016/s1053-2498(02)00557-0 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2003 Jul;22(7):738-44. doi: 
      10.1016/s1053-2498(02)00557-0.