PMID- 9743225
OWN - NLM
STAT- MEDLINE
DCOM- 19981001
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 18
IP  - 9
DP  - 1998 Sep
TI  - Atherogenic properties of enzymatically degraded LDL: selective induction of 
      MCP-1 and cytotoxic effects on human macrophages.
PG  - 1376-85
AB  - The mechanisms underlying the selective accumulation of macrophages in early 
      atherosclerotic lesions are poorly understood but are likely to be related to 
      specific properties of altered low density lipoprotein (LDL) deposited in the 
      subendothelium. Enzymatic, nonoxidative degradation of LDL converts the 
      lipoprotein to a potentially atherogenic moiety, enzymatically altered LDL 
      (E-LDL), which activates complement and is rapidly taken up by human macrophages 
      via a scavenger receptor-dependent pathway. Immunohistological evidence indicates 
      that E-LDL is present in an extracellular location in the early lesion. We report 
      that E-LDL causes massive release of monocyte chemotactic protein 1 (MCP-1) from 
      macrophages and that expression of interleukin 8 or RANTES remains unchanged. 
      Release of MCP-1 was preceded by a rapid expression of MCP-1 mRNA, which was 
      detectable after 15 minutes, reached maximum levels after 1 hour, and remained 
      detectable for 12 hours after exposure to concentrations as low as 10 microg/mL 
      E-LDL. MCP-1 mRNA induction and protein release by E-LDL exceeded that evoked by 
      oxidized LDL. Release of MCP-1 was dependent on de novo protein synthesis and on 
      the activity of tyrosine kinases. At higher concentrations, E-LDL, but not 
      oxidized LDL, exerted toxic effects on macrophages that in part appeared to be 
      due to apoptosis. The results show that E-LDL possesses major properties of an 
      atherogenic lipoprotein.
FAU - Klouche, M
AU  - Klouche M
AD  - Institute of Medical Microbiology and Hygiene, Johannes-Gutenberg University of 
      Mainz, Germany. klouche@mail.Uni-Mainz.de
FAU - Gottschling, S
AU  - Gottschling S
FAU - Gerl, V
AU  - Gerl V
FAU - Hell, W
AU  - Hell W
FAU - Husmann, M
AU  - Husmann M
FAU - Dorweiler, B
AU  - Dorweiler B
FAU - Messner, M
AU  - Messner M
FAU - Bhakdi, S
AU  - Bhakdi S
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 (Chemokine CCL2)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.7.49 (RNA-Directed DNA Polymerase)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.1.1.13 (Sterol Esterase)
RN  - EC 3.2.1.18 (Neuraminidase)
RN  - EC 3.4.21.4 (Trypsin)
SB  - IM
MH  - Arteriosclerosis/*etiology
MH  - Cell Death
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Hydrolases/*metabolism
MH  - Kinetics
MH  - Lipoproteins, LDL/*metabolism/*pharmacology
MH  - Macrophages/*drug effects/physiology
MH  - Neuraminidase/metabolism
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
MH  - RNA-Directed DNA Polymerase
MH  - Sterol Esterase/metabolism
MH  - Trypsin/metabolism
EDAT- 1998/09/22 00:00
MHDA- 1998/09/22 00:01
CRDT- 1998/09/22 00:00
PHST- 1998/09/22 00:00 [pubmed]
PHST- 1998/09/22 00:01 [medline]
PHST- 1998/09/22 00:00 [entrez]
AID - 10.1161/01.atv.18.9.1376 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 1998 Sep;18(9):1376-85. doi: 
      10.1161/01.atv.18.9.1376.