PMID- 7695193
OWN - NLM
STAT- MEDLINE
DCOM- 19950427
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 748
DP  - 1995 Jan 17
TI  - Enhanced expression of vascular matrix metalloproteinases induced in vitro by 
      cytokines and in regions of human atherosclerotic lesions.
PG  - 501-7
AB  - Dysregulated extracellular matrix (ECM) metabolism may contribute to vascular 
      remodeling during atherogenesis. The ability of vascular cells to synthesize the 
      components of ECM is well characterized, but less is known about their capacity 
      to degrade ECM and the factors that may regulate this process. We therefore 
      studied the expression of matrix metalloproteinases (MMPs), enzymes that degrade 
      various components of ECM, and of tissue inhibitors of MMPs (TIMPs) by untreated 
      or cytokine-stimulated human smooth muscle cells (SMC). Messenger RNA was studied 
      by Northern blotting, and proteins secreted in culture by SMC were identified by 
      immunoprecipitation. Gelatinolytic and caseinolytic activity of MMPs was detected 
      zymographically. SMC constitutively produced a 72 kDa type IV gelatinase (GL), 
      TIMP-1, and TIMP-2. Upon stimulation with IL1 or TNF alpha, SMC synthesized in 
      addition 92 kDa GL, stromelysin, and interstitial collagenase, MMPs that together 
      can degrade all of the ECM components. IL1 or TNF alpha did not alter the level 
      of TIMP mRNA and protein, suggesting that a net excess of MMP production under 
      these conditions may promote breakdown of the vascular ECM. To test the in vivo 
      relevance of these in vitro findings, we analyzed immunohistochemically normal 
      human arteries and carotid atheromas. Normal tissue and the medial layer 
      underlying lesions stained uniformly for 72 kDa GL and TIMPs 1 and 2. Lesions 
      showed regionally increased MMP expression: the shoulders of atherosclerotic 
      plaques contained stromelysin and 92 kDa GL associated with SMC, and clusters of 
      macrophage-derived foam cells associated with the lipid core stained intensely 
      for all MMPs studied. Endothelial cells covering atheroma or of the plaque 
      microvasculature contained interstitial collagenase. In pathological conditions 
      associated with local release of cytokines in the vessel wall, enhanced regional 
      expression of vascular MMPs may contribute to SMC migration and weakening of 
      matrix that would favor plaque rupture, events associated with the development or 
      complication of the atherosclerotic lesions.
FAU - Galis, Z S
AU  - Galis ZS
AD  - Brigham and Women's Hospital, Boston, Massachussetts, USA.
FAU - Muszynski, M
AU  - Muszynski M
FAU - Sukhova, G K
AU  - Sukhova GK
FAU - Simon-Morrissey, E
AU  - Simon-Morrissey E
FAU - Libby, P
AU  - Libby P
LA  - eng
GR  - HL34636-10/HL/NHLBI 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  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Glycoproteins)
RN  - 0 (Interleukin-1)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.- (Gelatinases)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Arteries/enzymology
MH  - Arteriosclerosis/*enzymology
MH  - Cells, Cultured
MH  - Extracellular Matrix/metabolism
MH  - Gelatinases/metabolism
MH  - Glycoproteins/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Interleukin-1/pharmacology
MH  - Metalloendopeptidases/*metabolism
MH  - Muscle, Smooth, Vascular/*enzymology
MH  - Tissue Inhibitor of Metalloproteinases
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1995/01/17 00:00
MHDA- 1995/01/17 00:01
CRDT- 1995/01/17 00:00
PHST- 1995/01/17 00:00 [pubmed]
PHST- 1995/01/17 00:01 [medline]
PHST- 1995/01/17 00:00 [entrez]
AID - 10.1111/j.1749-6632.1994.tb17348.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 1995 Jan 17;748:501-7. doi: 10.1111/j.1749-6632.1994.tb17348.x.