PMID- 10082471
OWN - NLM
STAT- MEDLINE
DCOM- 19990324
LR  - 20190706
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 84
IP  - 5
DP  - 1999 Mar 19
TI  - TIMP-4 is regulated by vascular injury in rats.
PG  - 498-504
AB  - The role of basement membrane-degrading matrix metalloproteinases (MMPs) in
      enabling vascular smooth muscle cell migration after vascular injury has been
      established in several animal models. In contrast, the role of their native
      inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), has
      remained unproven despite frequent coregulation of MMPs and TIMPs in other
      disease states. We have investigated the time course of expression and
      localization of TIMP-4 in rat carotid arteries 6 hours, 24 hours, 3 days, 7 days,
      and 14 days after balloon injury by in situ hybridization, immunohistochemistry, 
      and Western blot analysis. TIMP-4 protein was present in the adventitia of
      injured carotid arteries from 24 hours after injury. At 7 and 14 days after
      injury, widespread immunostaining for TIMP-4 was observed throughout the
      neointima, media, and adventitia of injured arteries. Western blot analysis
      confirmed the quantitative increase in TIMP-4 protein at 7 and 14 days. In situ
      hybridization detected increased expression of TIMP-4 as early as 24 hours after 
      injury and a marked induction in neointimal cells 7 days after injury. We then
      studied the effect of TIMP-4 protein on the migration of smooth muscle cells
      through a matrix-coated membrane in vitro and demonstrated a 53% reduction in
      invasion of rat vascular smooth muscle cells. These data and the temporal
      relationship between the upregulation of TIMP-4, its accumulation, and the onset 
      of collagen deposition suggest an important role for TIMP-4 in the proteolytic
      balance of the vasculature controlling both smooth muscle migration and collagen 
      accumulation in the injured arterial wall.
FAU - Dollery, C M
AU  - Dollery CM
AD  - Hatter Institute, University College London Hospitals, London, UK.
      c.dollery@ucl.ac.uk
FAU - McEwan, J R
AU  - McEwan JR
FAU - Wang, M
AU  - Wang M
FAU - Sang, Q A
AU  - Sang QA
FAU - Liu, Y E
AU  - Liu YE
FAU - Shi, Y E
AU  - Shi YE
LA  - eng
GR  - CA68064-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (tissue inhibitor of metalloproteinase-4)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Carotid Artery Injuries
MH  - Carotid Artery, Common/*metabolism
MH  - Catheterization
MH  - Cell Movement
MH  - Cells, Cultured
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Male
MH  - Muscle, Smooth, Vascular/cytology/injuries/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Wistar
MH  - Time Factors
MH  - Tissue Inhibitor of Metalloproteinases/*biosynthesis/genetics
EDAT- 1999/03/19 00:00
MHDA- 1999/03/19 00:01
CRDT- 1999/03/19 00:00
PHST- 1999/03/19 00:00 [pubmed]
PHST- 1999/03/19 00:01 [medline]
PHST- 1999/03/19 00:00 [entrez]
AID - 10.1161/01.res.84.5.498 [doi]
PST - ppublish
SO  - Circ Res. 1999 Mar 19;84(5):498-504. doi: 10.1161/01.res.84.5.498.