PMID- 10397688
OWN - NLM
STAT- MEDLINE
DCOM- 19990729
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 19
IP  - 7
DP  - 1999 Jul
TI  - Increased secretion of tissue inhibitors of metalloproteinases 1 and 2 from the 
      aortas of cholesterol fed rabbits partially counterbalances increased 
      metalloproteinase activity.
PG  - 1700-7
AB  - The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of 
      MMPs (TIMPs) plays an important role in extracellular matrix turnover and thereby 
      modulates atherosclerotic plaque development. MMP-1, -2, -3, and -9 activity is 
      increased by atherosclerosis, but the status of TIMPs is less clear. We therefore 
      compared secretion of TIMPs-1 and -2 from cultured aortic explants derived from 
      arch, middle, and distal portions of thoracic aortas of normal rabbits and 
      rabbits fed a 1% cholesterol diet for 8 weeks, using reverse zymography of 
      conditioned media. Cholesterol feeding significantly increased secretion of 
      TIMP-1 from arch and middle portions (both 2.6-fold), accompanied by 2.0- and 
      2.7-fold increases in TIMP-2, respectively. Atherosclerotic aortas exhibited 
      increased immunoreactive TIMP-1 and TIMP-2 in endothelial cells, smooth muscle 
      cells, and macrophages. Staining of extracellular matrix was also prominent 
      within the noncellular boundary region between fibrous cap and the lipid core, 
      and within the lipid core. Increased TIMP-2 staining was also found in the media 
      subjacent to the lipid core. In situ gelatin zymography demonstrated excess MMP 
      activity within the plaque with partial inhibition in the lipid core base and 
      subjacent media, consistent with the distribution of TIMPs. Casein zymography and 
      in situ zymography demonstrated that increased caseinolytic activity was confined 
      to the pericellular zones of macrophages within the lipid core, again consistent 
      with its restriction by TIMPs. In summary, atherosclerosis increases TIMP 
      expression, which counterbalances, in part, increased MMP activity.
FAU - Zaltsman, A B
AU  - Zaltsman AB
AD  - Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol, 
      UK. a.b.zaltsman@bristol.ac.uk
FAU - George, S J
AU  - George SJ
FAU - Newby, A C
AU  - Newby AC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Cholesterol, Dietary)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 3.4.24.- (Gelatinases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Aorta/*metabolism
MH  - Arteriosclerosis/*metabolism
MH  - Cholesterol, Dietary/*administration & dosage
MH  - Gelatinases/*biosynthesis
MH  - Immunohistochemistry
MH  - Male
MH  - Matrix Metalloproteinase 3/*biosynthesis
MH  - Rabbits
MH  - Tissue Inhibitor of Metalloproteinase-1/*metabolism
MH  - Tissue Inhibitor of Metalloproteinase-2/*metabolism
EDAT- 1999/07/09 00:00
MHDA- 1999/07/09 00:01
CRDT- 1999/07/09 00:00
PHST- 1999/07/09 00:00 [pubmed]
PHST- 1999/07/09 00:01 [medline]
PHST- 1999/07/09 00:00 [entrez]
AID - 10.1161/01.atv.19.7.1700 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 1999 Jul;19(7):1700-7. doi: 
      10.1161/01.atv.19.7.1700.