PMID- 26969796
OWN - NLM
STAT- MEDLINE
DCOM- 20171229
LR  - 20220129
IS  - 1469-445X (Electronic)
IS  - 0958-0670 (Linking)
VI  - 101
IP  - 11
DP  - 2016 Nov 1
TI  - Metalloproteinase production from macrophages - a perfect storm leading to 
      atherosclerotic plaque rupture and myocardial infarction.
PG  - 1327-1337
LID - 10.1113/EP085567 [doi]
AB  - What is the topic of this review? The review discusses how in atherosclerotic 
      plaques, a combination of inflammatory mediators together with loss of anti 
      inflammatory factors is most likely to be responsible for the excess of MMP over 
      TIMP expression that causes plaque rupture and myocardial infarction. What 
      advances does it highlight? Regulation of matrix metalloproteinases (MMPs) and 
      tissue inhibitors of MMP (TIMPs) is divergent between human and mouse 
      macrophages. There is prostaglandin E(2) -dependent and -independent regulation. 
      Inflammatory cytokines act through distinct (albeit overlapping) signalling 
      pathways to elicit different patterns of MMP and TIMP expression. Transcriptional 
      and epigenetic regulation occurs. Matrix metalloproteinases (MMPs) produced from 
      macrophages contribute to plaque rupture, atherothrombosis and myocardial 
      infarction. New treatments could emerge from defining the mediators and 
      underlying mechanisms. In human monocytes, prostaglandin E(2) (PGE(2) ) 
      stimulates MMP production, and inflammatory mediators such as tumour necrosis 
      factor alpha, interleukin-1 and Toll-like receptor ligands can act either through or 
      independently of PGE(2) . Differentiation of human monocytes to non-foamy 
      macrophages increases constitutive expression of MMP-7, -8, -9, -14 and -19 and 
      tissue inhibitor of MMP (TIMP)-1 to -3 through unknown, PGE(2) -independent 
      mechanisms. Human macrophages express more MMP-1, -7 and -9 and TIMP-3 and less 
      MMP-12 and -13 than mouse macrophages. Inflammatory mediators working through 
      activator protein-1 and nuclear factor-kappaB transcription factor pathways 
      upregulate MMP-1, -3, -10, -12 and -14 in human macrophages (MMP-9, -12 and -13 
      in mice), and studies with plaque tissue sections and isolated foam cells confirm 
      this conclusion in vivo. Classical activation with granulocyte-macrophage 
      colony-stimulating factor upregulates MMP-12, whereas interferon-gamma upregulates 
      MMP-12, -14 and -25 and downregulates TIMP-3 in human but not mouse macrophages. 
      Alternative activation with interleukin-4 markedly stimulates the expression of 
      only MMP-12 in humans and MMP-19 in mice. The anti-inflammatory cytokines 
      interleukin-10 and transforming growth factor-beta decrease production of several 
      MMPs. Epigenetic upregulation of MMP-14 during foam cell formation or by 
      granulocyte-macrophage colony-stimulating factor occurs by decreasing miRNA-24. A 
      'perfect storm' caused by a combination of these mechanisms is most likely to 
      promote MMP-mediated macrophage invasion, tissue destruction and atherosclerotic 
      plaque rupture.
CI  - (c) 2016 The Authors. Experimental Physiology (c) 2016 The Physiological Society.
FAU - Newby, Andrew C
AU  - Newby AC
AD  - University of Bristol, School of Clinical Sciences and Bristol Heart Institute, 
      Bristol, UK. a.newby@bris.ac.uk.
LA  - eng
GR  - RG/09/006/27918/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20160505
PL  - England
TA  - Exp Physiol
JT  - Experimental physiology
JID - 9002940
RN  - 0 (Cytokines)
RN  - EC 3.4.- (Metalloproteases)
SB  - IM
CIN - Exp Physiol. 2016 Nov 1;101(11):1325-1326. PMID: 27800668
MH  - Animals
MH  - Cytokines/metabolism
MH  - Humans
MH  - Inflammation/metabolism/pathology
MH  - Macrophages/*metabolism
MH  - Metalloproteases/*metabolism
MH  - Myocardial Infarction/*metabolism/*pathology
MH  - Plaque, Atherosclerotic/*metabolism/*pathology
EDAT- 2016/11/02 06:00
MHDA- 2017/12/30 06:00
CRDT- 2016/03/13 06:00
PHST- 2015/12/26 00:00 [received]
PHST- 2016/03/08 00:00 [accepted]
PHST- 2016/11/02 06:00 [pubmed]
PHST- 2017/12/30 06:00 [medline]
PHST- 2016/03/13 06:00 [entrez]
AID - 10.1113/EP085567 [doi]
PST - ppublish
SO  - Exp Physiol. 2016 Nov 1;101(11):1327-1337. doi: 10.1113/EP085567. Epub 2016 May 
      5.