PMID- 12816876
OWN - NLM
STAT- MEDLINE
DCOM- 20040204
LR  - 20190508
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 23
IP  - 9
DP  - 2003 Sep 1
TI  - Low-level endotoxin induces potent inflammatory activation of human blood 
      vessels: inhibition by statins.
PG  - 1576-82
AB  - BACKGROUND: Low-level endotoxemia (ie, >or=50 pg/mL) in apparently healthy 
      subjects was recently identified as a powerful, independent risk factor for 
      atherosclerosis. METHODS AND RESULTS: We treated human saphenous veins (HSVs) 
      with low levels of endotoxin. Release of the proinflammatory chemokines 
      interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) was measured 
      by ELISA. Superoxide was determined by using the fluorescent probe 
      dihydroethidium (HE), and monocyte binding was assessed with calcein-labeled 
      U-937 cells. Three- to 4-fold increases in MCP-1 and IL-8 release were observed 
      at endotoxin concentrations of 100 pg/mL; these increases were inhibited by the 
      3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin. Studies 
      in cultured endothelial cells suggest that the mechanism is related to inhibition 
      of isoprenylation (ie, geranylgeranylation) rather than cholesterol formation. 
      Endotoxin produced dose-dependent increases in HE fluorescence that were 
      inhibited by the superoxide dismutase mimics Tiron and MnTBAP. Endotoxin potently 
      induced U-937 cell binding to HSV; binding was inhibited by both Tiron and 
      atorvastatin. Toll-like receptor-4 expression was detected in cultured HSV 
      endothelial and smooth muscle cells and in intact HSV. CONCLUSIONS: Clinically 
      relevant levels of endotoxin, as reported in ambulatory populations, have 
      profound inflammatory effects on intact HSV. Inhibition of endotoxin-induced 
      vascular inflammation might contribute to the beneficial effects of statins in 
      treating atherosclerosis.
FAU - Rice, James B
AU  - Rice JB
AD  - Department of Internal Medicine, University of Iowa College of Medicine, Iowa 
      City, IA 52242, USA.
FAU - Stoll, Lynn L
AU  - Stoll LL
FAU - Li, Wei-Gen
AU  - Li WG
FAU - Denning, Gerene M
AU  - Denning GM
FAU - Weydert, Jamie
AU  - Weydert J
FAU - Charipar, Elizabeth
AU  - Charipar E
FAU - Richenbacher, Wayne E
AU  - Richenbacher WE
FAU - Miller, Francis J Jr
AU  - Miller FJ Jr
FAU - Weintraub, Neal L
AU  - Weintraub NL
LA  - eng
GR  - K08 HL003669-04/HL/NHLBI NIH HHS/United States
GR  - K08 HL003669-05/HL/NHLBI NIH HHS/United States
GR  - HL62984/HL/NHLBI NIH HHS/United States
GR  - HL49264/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030619
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Chemokine CCL2)
RN  - 0 (Endotoxins)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Interleukin-8)
SB  - IM
MH  - Blood Vessels/drug effects/metabolism/*physiology
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/metabolism
MH  - Coronary Vessels/cytology/drug effects/metabolism/physiology
MH  - Endothelium, Vascular/cytology/drug effects/metabolism/physiology
MH  - Endotoxins/*antagonists & inhibitors/*immunology
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Inflammation/etiology/metabolism/prevention & control
MH  - Interleukin-8/metabolism
MH  - Muscle, Smooth, Vascular/cytology/drug effects/metabolism/physiology
MH  - Saphenous Vein/drug effects/metabolism/physiology
MH  - U937 Cells/metabolism
EDAT- 2003/06/21 05:00
MHDA- 2004/02/05 05:00
CRDT- 2003/06/21 05:00
PHST- 2003/06/21 05:00 [pubmed]
PHST- 2004/02/05 05:00 [medline]
PHST- 2003/06/21 05:00 [entrez]
AID - 01.ATV.0000081741.38087.F9 [pii]
AID - 10.1161/01.ATV.0000081741.38087.F9 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1576-82. doi: 
      10.1161/01.ATV.0000081741.38087.F9. Epub 2003 Jun 19.