PMID- 10729379
OWN - NLM
STAT- MEDLINE
DCOM- 20000516
LR  - 20190718
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 149
IP  - 2
DP  - 2000 Apr
TI  - Small oxidative changes in atherogenic LDL concentrations irreversibly regulate 
      adhesiveness of human endothelial cells: effect of the lazaroid U74500A.
PG  - 295-302
AB  - The adherence of monocytes to the endothelium is an early event in atherogenesis 
      which is modulated by low density lipoproteins (LDL). We analyzed the effect of 
      atherogenic LDL levels (180 mg cholesterol/dl, for 24 h) with minimal oxidative 
      modifications (thiobarbituric-acid-reactive-substances (TBARS) concentration 
      between 1.2+/-0.1 and 2.5+/-0.3 nmol of malonaldehyde bis-diethyl acetal (MDA) 
      per mg protein) on human umbilical vein endothelial cell (HUVEC) adhesive 
      properties. We used native LDL (n-LDL), and LDL exposed to spontaneous oxidation 
      without antioxidants (mox-LDL) or with 20 micromol/l of the antioxidant butylated 
      hydroxytoluene (BHT-LDL) or 10 micromol/l U74500A (U74500A-LDL), a scavenger of 
      free radicals. Thiobarbituric-acid-reactive-substances (TBARS) levels were 
      significantly higher in mox-LDL (2.5+/-0.3 nmol MDA/mg protein) than in BHT-LDL 
      (1.6+/-0.2), U74500A-LDL (1.2+/-0.1) or in n-LDL (1.3+/-0.1). mox-LDL induced the 
      greatest adhesion of U937 cells to HUVEC (103+/-9% over controls) followed by 
      BHT-LDL (75+/-10%), U74500A-LDL (36+/-9%) and n-LDL (35+/-3%). The lazaroid 
      U74500A efficiently protected U74500A-LDL against oxidative damage and prevented 
      endothelial adhesiveness associated with this LDL modification, inducing adhesion 
      effects similar to those of n-LDL. However, U74500A could not reverse the 
      adhesion induced by previously oxidized LDL (mox-LDL). LDL did not induce the 
      expression of the intercellular cell adhesion molecule-1 (ICAM-1), vascular cell 
      adhesion molecule-1 (VCAM-1) or E-selectin, but it produced a downregulation of 
      endothelial nitric oxide synthase (NOS III) mRNA levels. Thus, adhesiveness of 
      human endothelial cells (EC) exposed to atherogenic concentrations of LDL is 
      closely modulated by minimal changes in LDL oxidative state, and could be related 
      to a downregulation of NOS III.
FAU - Colome, C
AU  - Colome C
AD  - Cardiovascular Research Center, IIBB/CSIC-Institut de Recerca del Hospital de la 
      Santa Creu i Sant Pau, Avda. Sant Antoni Maria Claret #167, 08025, Barcelona, 
      Spain.
FAU - Martinez-Gonzalez, J
AU  - Martinez-Gonzalez J
FAU - Vidal, F
AU  - Vidal F
FAU - de Castellarnau, C
AU  - de Castellarnau C
FAU - Badimon, L
AU  - Badimon L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Antioxidants)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Pregnatrienes)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - IDW4RCM01L (U 74500A)
SB  - IM
MH  - Analysis of Variance
MH  - Antioxidants/*pharmacology
MH  - Arteriosclerosis/metabolism/pathology
MH  - Cell Adhesion/drug effects
MH  - Cells, Cultured
MH  - Endothelium, Vascular/cytology/*drug effects/metabolism
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/*drug effects
MH  - Lipid Peroxidation/*drug effects/physiology
MH  - Lipoproteins, LDL/drug effects/*metabolism
MH  - Pregnatrienes/*pharmacology
MH  - Probability
MH  - Reference Values
MH  - Umbilical Veins
MH  - Vascular Cell Adhesion Molecule-1/*drug effects
EDAT- 2000/03/24 09:00
MHDA- 2000/05/20 09:00
CRDT- 2000/03/24 09:00
PHST- 2000/03/24 09:00 [pubmed]
PHST- 2000/05/20 09:00 [medline]
PHST- 2000/03/24 09:00 [entrez]
AID - S0021-9150(99)00338-X [pii]
AID - 10.1016/s0021-9150(99)00338-x [doi]
PST - ppublish
SO  - Atherosclerosis. 2000 Apr;149(2):295-302. doi: 10.1016/s0021-9150(99)00338-x.