PMID- 17383753
OWN - NLM
STAT- MEDLINE
DCOM- 20080221
LR  - 20181201
IS  - 1874-1754 (Electronic)
IS  - 0167-5273 (Linking)
VI  - 124
IP  - 1
DP  - 2008 Feb 20
TI  - Fluvastatin reduces increased blood monocyte Toll-like receptor 4 expression in 
      whole blood from patients with chronic heart failure.
PG  - 80-5
AB  - BACKGROUND: Innate immune activation mediated by myocardial Toll-like receptors 
      (TLRs) is involved in cardiovascular disease. The function and role of TLRs on 
      peripheral leukocytes in human chronic heart failure (CHF) are not known. 
      METHODS: We measured whole blood TLR4 and TLR2 expressions in 28 patients with 
      CHF (64+/-2 years, New York Heart Association [NYHA] functional class 2.2+/-0.1, 
      left ventricular (LV) ejection fraction 32+/-2%) and 13 healthy subjects of 
      similar age and gender. RESULTS: As assessed by flow cytometry, TLR4 and TLR2 
      were detected on CD14+ monocytes. Unstimulated monocyte TLR4 expression was 
      significantly higher in CHF patients compared to controls (mean fluorescence 
      intensity, 3.57+/-0.57 vs. 1.72+/-0.32, p<0.05). TLR2 expressions were similar in 
      CHF patients and control subjects (p=0.5). TLR4 levels correlated with the 
      severity of CHF (NYHA class I/II: 2.66+/-0.40, and NYHA class III/IV: 
      5.08+/-1.24, p<0.01) and with serum lipid levels (total cholesterol, r=-0.44, 
      p<0.01 and high-density lipoprotein, r=-0.68, p<0.001). After stimulation of 
      monocytes by lipopolysaccharide (LPS, 10 ng/ml, 3 h), activated TLR4 was higher 
      in CHF patients (p<0.05). Pre-incubation with fluvastatin for 24 h inhibited 
      dose-dependently ex vivo monocyte TLR4 and TLR2 expressions (p<0.001). 
      CONCLUSIONS: This study suggests that upregulation of monocyte TLR4 may 
      contribute to the pathophysiology of chronic heart failure. Fluvastatin may 
      prevent excessive innate immune response in vitro in chronic heart failure by 
      inhibition of monocyte Toll-like receptor signaling.
FAU - Foldes, Gabor
AU  - Foldes G
AD  - Department of Clinical Cardiology, National Heart and Lung Institute, Imperial 
      College School of Medicine, London, UK. foldesg@bel1.sote.hu
FAU - von Haehling, Stephan
AU  - von Haehling S
FAU - Okonko, Darlington O
AU  - Okonko DO
FAU - Jankowska, Ewa A
AU  - Jankowska EA
FAU - Poole-Wilson, Philip A
AU  - Poole-Wilson PA
FAU - Anker, Stefan D
AU  - Anker SD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070326
PL  - Netherlands
TA  - Int J Cardiol
JT  - International journal of cardiology
JID - 8200291
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 4L066368AS (Fluvastatin)
SB  - IM
MH  - Aged
MH  - Analysis of Variance
MH  - Case-Control Studies
MH  - Chronic Disease
MH  - Fatty Acids, Monounsaturated/*pharmacology
MH  - Female
MH  - Flow Cytometry
MH  - Fluvastatin
MH  - Heart Failure/*blood/*drug therapy
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Indoles/*pharmacology
MH  - Male
MH  - Middle Aged
MH  - Monocytes/drug effects/*metabolism
MH  - Statistics, Nonparametric
MH  - Toll-Like Receptor 4/*blood
EDAT- 2007/03/27 09:00
MHDA- 2008/02/22 09:00
CRDT- 2007/03/27 09:00
PHST- 2006/06/10 00:00 [received]
PHST- 2006/10/26 00:00 [revised]
PHST- 2006/12/30 00:00 [accepted]
PHST- 2007/03/27 09:00 [pubmed]
PHST- 2008/02/22 09:00 [medline]
PHST- 2007/03/27 09:00 [entrez]
AID - S0167-5273(07)00340-3 [pii]
AID - 10.1016/j.ijcard.2006.12.024 [doi]
PST - ppublish
SO  - Int J Cardiol. 2008 Feb 20;124(1):80-5. doi: 10.1016/j.ijcard.2006.12.024. Epub 
      2007 Mar 26.