PMID- 23131422
OWN - NLM
STAT- MEDLINE
DCOM- 20130619
LR  - 20121123
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Linking)
VI  - 61
IP  - 1
DP  - 2013 Jan
TI  - Elevated serum MMP-9/TIMP-1 ratio in patients with homozygous familial 
      hypercholesterolemia: effects of LDL-apheresis.
PG  - 194-8
LID - S1043-4666(12)00708-9 [pii]
LID - 10.1016/j.cyto.2012.09.016 [doi]
AB  - OBJECTIVE: Matrix degradation within an atherosclerotic plaque is an important 
      pathogenic factor in atherosclerosis, and is largely modulated by the balance 
      between matrix metalloproteinases (MMPs) and their endogenous inhibitors (i.e., 
      tissue inhibitor of MMPs [TIMPs]). Familial hypercholesterolemia (FH) is a rare 
      inherited disorder associated with premature coronary heart disease. The aim of 
      the present study was to examine MMP-9 and TIMP-1 on plasma and cellular mRNA 
      levels in homozygous FH patients (n=7) compared with age- and sex-matched 
      heterozygous FH patients (n=6), and with healthy subjects (n=7), and to test 
      whether once-weekly LDL-apheresis (three consecutive sessions) of homozygous FH 
      patients show short-term effects on these variables. RESULTS: The main findings 
      were that (i) Compared to healthy control subjects, homozygous FH patients have 
      significantly higher serum levels of MMP-9 and lower levels of TIMP-1, and 
      consequently significantly higher MMP-9/TIMP-1 ratio, potentially reflecting 
      higher MMP-9 activity. (ii) Peripheral blood mononuclear cells (PBMC) isolated 
      from FH homozygotes have significantly higher mRNA levels of MMP-9 compared to 
      cells from heterozygotes. (iii) TNFalpha-stimulated PBMC from FH homozygotes released 
      borderline-significantly more MMP-9 than cells from heterozygotes and healthy 
      controls. (iv) LDL-apheresis (one day before treatment versus fifteen days later, 
      on the day after the weekly treatment) had no significant short-term effect on 
      any of the MMP-9 and TIMP-1 variables measured in serum and cells. CONCLUSIONS: 
      The data may suggest that homozygous FH patients have an enhanced matrix 
      degrading potential as compared with heterozygous FH patients and healthy 
      controls, potentially contributing to the increased cardiovascular risk observed 
      in these patients.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Nenseter, Marit S
AU  - Nenseter MS
AD  - Lipid Clinic, Oslo University Hospital Rikshospitalet, and Department of 
      Nutrition, Institute for Basic Medical Sciences, University of Oslo, Oslo, 
      Norway. marit.s.nenseter@rr-research.no
FAU - Narverud, Ingunn
AU  - Narverud I
FAU - Graesdal, Asgeir
AU  - Graesdal A
FAU - Bogsrud, Martin P
AU  - Bogsrud MP
FAU - Halvorsen, Bente
AU  - Halvorsen B
FAU - Ose, Leiv
AU  - Ose L
FAU - Aukrust, Pal
AU  - Aukrust P
FAU - Holven, Kirsten B
AU  - Holven KB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121104
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Atherosclerosis/immunology
MH  - Blood Component Removal
MH  - Cardiovascular Diseases/genetics
MH  - Child
MH  - Female
MH  - Humans
MH  - Hyperlipoproteinemia Type II/*blood/genetics
MH  - Inflammation
MH  - Leukocytes, Mononuclear/*cytology/drug effects
MH  - Lipoproteins, LDL/*blood/genetics
MH  - Male
MH  - Matrix Metalloproteinase 9/*blood/genetics
MH  - Middle Aged
MH  - RNA, Messenger/analysis
MH  - Tissue Inhibitor of Metalloproteinase-1/*blood
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Young Adult
EDAT- 2012/11/08 06:00
MHDA- 2013/06/20 06:00
CRDT- 2012/11/08 06:00
PHST- 2012/03/20 00:00 [received]
PHST- 2012/09/03 00:00 [revised]
PHST- 2012/09/23 00:00 [accepted]
PHST- 2012/11/08 06:00 [entrez]
PHST- 2012/11/08 06:00 [pubmed]
PHST- 2013/06/20 06:00 [medline]
AID - S1043-4666(12)00708-9 [pii]
AID - 10.1016/j.cyto.2012.09.016 [doi]
PST - ppublish
SO  - Cytokine. 2013 Jan;61(1):194-8. doi: 10.1016/j.cyto.2012.09.016. Epub 2012 Nov 4.