PMID- 22326338
OWN - NLM
STAT- MEDLINE
DCOM- 20120913
LR  - 20121115
IS  - 1879-3649 (Electronic)
IS  - 1537-1891 (Linking)
VI  - 56
IP  - 5-6
DP  - 2012 May-Jun
TI  - Matrix metalloproteinase inhibition therapy for vascular diseases.
PG  - 232-44
LID - 10.1016/j.vph.2012.01.007 [doi]
AB  - The matrix metalloproteinases (MMPs) are 23 secreted or cell surface proteases 
      that act together and with other protease classes to turn over the extracellular 
      matrix, cleave cell surface proteins and alter the function of many secreted 
      bioactive molecules. In the vasculature MMPs influence the migration 
      proliferation and apoptosis of vascular smooth muscle, endothelial cells and 
      inflammatory cells, thereby affecting intima formation, atherosclerosis and 
      aneurysms, as substantiated in clinical and mouse knockout and transgenic 
      studies. Prominent counterbalancing roles for MMPs in tissue destruction and 
      repair emerge from these experiments. Naturally occurring tissue inhibitors of 
      MMPs (TIMPs), pleiotropic mediators such as tetracyclines, chemically-synthesised 
      small molecular weight MMP inhibitors (MMPis) and inhibitory antibodies have all 
      shown effects in animal models of vascular disease but only doxycycline has been 
      evaluated extensively in patients. A limitation of broad specificity MMPis is 
      that they prevent both matrix degradation and tissue repair functions of 
      different MMPs. Hence MMPis with more restricted specificity have been developed 
      and recent studies in models of atherosclerosis accurately replicate the 
      phenotypes of the corresponding gene knockouts. This review documents the 
      established actions of MMPs and their inhibitors in vascular pathologies and 
      considers the prospects for translating these findings into new treatments.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Newby, Andrew C
AU  - Newby AC
AD  - Bristol Heart Institute, University of Bristol, UK. a.newby@bris.ac.uk
LA  - eng
GR  - British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120201
PL  - United States
TA  - Vascul Pharmacol
JT  - Vascular pharmacology
JID - 101130615
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
SB  - IM
MH  - Animals
MH  - Aortic Aneurysm, Abdominal/drug therapy/physiopathology
MH  - Atherosclerosis/drug therapy/physiopathology
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/*pharmacology
MH  - Extracellular Matrix/metabolism
MH  - Humans
MH  - *Matrix Metalloproteinase Inhibitors
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Vascular Diseases/*drug therapy/physiopathology
EDAT- 2012/02/14 06:00
MHDA- 2012/09/14 06:00
CRDT- 2012/02/14 06:00
PHST- 2011/11/15 00:00 [received]
PHST- 2012/01/23 00:00 [revised]
PHST- 2012/01/25 00:00 [accepted]
PHST- 2012/02/14 06:00 [entrez]
PHST- 2012/02/14 06:00 [pubmed]
PHST- 2012/09/14 06:00 [medline]
AID - S1537-1891(12)00031-6 [pii]
AID - 10.1016/j.vph.2012.01.007 [doi]
PST - ppublish
SO  - Vascul Pharmacol. 2012 May-Jun;56(5-6):232-44. doi: 10.1016/j.vph.2012.01.007. 
      Epub 2012 Feb 1.