PMID- 16728689
OWN - NLM
STAT- MEDLINE
DCOM- 20060718
LR  - 20181201
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 37
IP  - 7
DP  - 2006 Jul
TI  - Impaired inhibitory effect of interleukin-10 on the balance between matrix 
      metalloproteinase-9 and its inhibitor in mononuclear cells from 
      hyperhomocysteinemic subjects.
PG  - 1731-6
AB  - BACKGROUND AND PURPOSE: Homocysteine has been linked to increased risk of 
      ischemic stroke and other cardiovascular events, but the mechanism by which 
      elevated plasma levels of homocysteine promotes atherogenesis remains unclear. 
      Matrix degradation, partly regulated by the balance between matrix 
      metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), plays an 
      important role in atherogenesis and plaque destabilization, and we hypothesized 
      an imbalance between MMPs and TIMPs in hyperhomocysteinemia. METHODS: Serum MMP-9 
      and TIMP-1 was measured in 12 hyperhomocysteinemic and 12 control subjects. The 
      release of MMP-9 and TIMP-1, with and without interleukin-10 (IL-10), and the 
      effect of IL-10 on signal transducer and activator of transcription 3 (STAT3) 
      phosphorylation were measured in peripheral blood mononuclear cells (PBMCs) from 
      hyperhomocysteinemic and control subjects. RESULTS: Our main findings were: (1) 
      hyperhomocysteinemic subjects had raised serum levels of MMP-9 and MMP-9/TIMP-1 
      ratio comparing healthy controls; (2) although IL-10 markedly suppressed MMP-9 
      release from PBMCs in controls, no or only minor effect was seen in 
      hyperhomocysteinemic subjects; (3) although IL-10 enhanced TIMP-1 levels in PBMCs 
      from both hyperhomocysteinemic and control subjects, the increase was more 
      prominent in controls, resulting in a marked difference in IL-10-induced changes 
      in MMP-9/TIMP-1 ratio between these 2 groups; and (4) comparing PBMCs from 
      controls, cells from hyperhomocysteinemic individuals had impaired IL-10-induced 
      STAT3 phosphorylation. CONCLUSIONS: Our findings suggest an attenuated inhibitory 
      response to IL-10 on MMP-9 activity in hyperhomocysteinemic subjects, potentially 
      promoting atherogenesis and plaque instability, representing a novel explanation 
      for increased risk for atherosclerotic disease in these individuals.
FAU - Holven, Kirsten B
AU  - Holven KB
AD  - Lipid Clinic, Rikshospitalet University Hospital, Oslo, Norway. 
      kirsten.holven@medisin.uio.no
FAU - Halvorsen, Bente
AU  - Halvorsen B
FAU - Bjerkeli, Vigdis
AU  - Bjerkeli V
FAU - Damas, Jan Kristian
AU  - Damas JK
FAU - Retterstol, Kjetil
AU  - Retterstol K
FAU - Morkrid, Lars
AU  - Morkrid L
FAU - Ose, Leiv
AU  - Ose L
FAU - Aukrust, Pal
AU  - Aukrust P
FAU - Nenseter, Marit S
AU  - Nenseter MS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060525
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-10)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 1)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Adult
MH  - Atherosclerosis/epidemiology/etiology
MH  - Cells, Cultured/drug effects/metabolism
MH  - Female
MH  - Humans
MH  - Hyperhomocysteinemia/*blood/complications/enzymology
MH  - Interleukin-10/pharmacology/*physiology
MH  - Janus Kinase 1
MH  - Leukocytes, Mononuclear/drug effects/metabolism
MH  - Male
MH  - Matrix Metalloproteinase 9/biosynthesis/*blood/genetics/metabolism
MH  - Middle Aged
MH  - Phosphorylation
MH  - Protein Processing, Post-Translational
MH  - Protein-Tyrosine Kinases/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Interleukin/biosynthesis/genetics
MH  - Receptors, Interleukin-10
MH  - Risk
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction
MH  - Tissue Inhibitor of Metalloproteinase-1/biosynthesis/*blood/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/analysis
EDAT- 2006/05/27 09:00
MHDA- 2006/07/19 09:00
CRDT- 2006/05/27 09:00
PHST- 2006/05/27 09:00 [pubmed]
PHST- 2006/07/19 09:00 [medline]
PHST- 2006/05/27 09:00 [entrez]
AID - 01.STR.0000226465.84561.cb [pii]
AID - 10.1161/01.STR.0000226465.84561.cb [doi]
PST - ppublish
SO  - Stroke. 2006 Jul;37(7):1731-6. doi: 10.1161/01.STR.0000226465.84561.cb. Epub 2006 
      May 25.