PMID- 10869259
OWN - NLM
STAT- MEDLINE
DCOM- 20000719
LR  - 20220317
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 101
IP  - 25
DP  - 2000 Jun 27
TI  - Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of monocyte 
      chemoattractant protein-1 and monocyte adhesion to human coronary artery 
      endothelial cells.
PG  - 2889-95
AB  - BACKGROUND: We have recently demonstrated a lectin-like receptor for oxidized 
      (ox)-LDL (LOX-1) in human coronary artery endothelial cells (HCAECs). This 
      receptor is upregulated by ox-LDL. The present study examined the significance of 
      LOX-1 in monocyte adhesion to HCAECs and endothelial injury in response to 
      ox-LDL. METHODS AND RESULTS: HCAECs were incubated in the presence of antisense 
      oligodeoxynucleotides to the 5'-coding sequence of the human LOX-1 gene (0.5 
      microm/L). Basal LOX-1 mRNA and protein were suppressed by antisense LOX-1. 
      Ox-LDL-mediated upregulation of LOX-1 was also suppressed by antisense LOX-1. 
      Incubation of HCAECs with ox-LDL (40 microg/mL) for 24 hours markedly increased 
      monocyte chemoattractant protein-1 (MCP-1) mRNA and protein expression as well as 
      monocyte adhesion to HCAECs (P<0.01). After 48 hours of preincubation of HCAECs 
      with antisense LOX-1, ox-LDL-mediated upregulation of MCP-1 and monocyte adhesion 
      to HCAECs both were suppressed (P<0.01), whereas sense LOX-1 had no effect. 
      Whereas antisense or sense LOX-1 alone (both 0.5 nmol/L) did not injure the 
      cells, antisense LOX-1, but not sense LOX-1, reduced ox-LDL-mediated HCAEC 
      injury, determined as LDH release (P<0.01). Activation of mitogen-activated 
      protein kinase (MAPK) may play a critical role in signal transduction in 
      ox-LDL-mediated alteration in MCP-1 expression, since antisense LOX-1, but not 
      the sense LOX-1, completely inhibited the ox-LDL-induced MAPK activation. 
      CONCLUSIONS: These observations with the first use of a specific antisense to 
      human LOX-1 mRNA suggest that LOX-1 is a key factor in ox-LDL-mediated monocyte 
      adhesion to HCAECs.
FAU - Li, D
AU  - Li D
AD  - Departments of Medicine and Physiology, University of Florida and VA Medical 
      Center, Gainesville, FL 32610, USA.
FAU - Mehta, J L
AU  - Mehta JL
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (OLR1 protein, human)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Receptors, LDL)
RN  - 0 (Receptors, Oxidized LDL)
RN  - 0 (Scavenger Receptors, Class E)
RN  - 0 (oxidized low density lipoprotein)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Cell Adhesion/drug effects/physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Coronary Vessels/drug effects/metabolism/pathology/*physiopathology
MH  - Endothelium, Vascular/drug effects/metabolism/pathology/*physiopathology
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Lipoproteins, LDL/pharmacology/*physiology
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Monocytes/*physiology
MH  - Oligonucleotides, Antisense/metabolism/pharmacology
MH  - Receptors, LDL/antagonists & inhibitors/genetics/*physiology
MH  - Receptors, Oxidized LDL
MH  - Scavenger Receptors, Class E
MH  - Up-Regulation/drug effects
EDAT- 2000/06/28 00:00
MHDA- 2000/07/25 00:00
CRDT- 2000/06/28 00:00
PHST- 2000/06/28 00:00 [pubmed]
PHST- 2000/07/25 00:00 [medline]
PHST- 2000/06/28 00:00 [entrez]
AID - 10.1161/01.cir.101.25.2889 [doi]
PST - ppublish
SO  - Circulation. 2000 Jun 27;101(25):2889-95. doi: 10.1161/01.cir.101.25.2889.