PMID- 18483405
OWN - NLM
STAT- MEDLINE
DCOM- 20080925
LR  - 20211020
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 28
IP  - 8
DP  - 2008 Aug
TI  - HDL-associated lysosphingolipids inhibit NAD(P)H oxidase-dependent monocyte 
      chemoattractant protein-1 production.
PG  - 1542-8
LID - 10.1161/ATVBAHA.107.161042 [doi]
AB  - OBJECTIVE: High-density lipoprotein (HDL) levels are inversely proportional to 
      the risk of atherosclerosis, but mechanisms of HDL atheroprotection remain 
      unclear. Monocyte chemoatractant protein-1 (MCP-1) constitutes an early component 
      of inflammatory response in atherosclerosis. Here we investigated the influence 
      of HDL on MCP-1 production in vascular smooth muscle cells (VSMCs) and rat aortic 
      explants. METHODS AND RESULTS: HDL inhibited the thrombin-induced production of 
      MCP-1 in a concentration-dependent manner. The HDL-dependent inhibition of MCP-1 
      production was accompanied by the suppression of reactive oxygen species (ROS), 
      which regulate the MCP-1 production in VSMCs. HDL inhibited NAD(P)H oxidase, the 
      preponderant source of ROS in the vasculature, and prevented the activation of 
      Rac1, which precedes NAD(P)H-oxidase activation. The HDL capacity to inhibit 
      MCP-1 production, ROS generation, and NAD(P)H-oxidase activation was emulated by 
      sphingosine 1-phosphate (S1P) and sphingosylphosphorylcholine (SPC), two 
      lysosphingolipids present in HDL, but not by apolipoprotein A-I. HDL-, S1P-, and 
      SPC-induced inhibition of MCP-1 production was attenuated in VSMCs pretreated 
      with VPC23019, an antagonist of lysosphingolipid receptors S1P(1) and S1P(3), but 
      not by JTE013, an antagonist of S1P(2). In addition, HDL, S1P, and SPC failed to 
      inhibit MCP1 production and ROS generation in aortas from S1P(3)- and 
      SR-B1-deficient mice. CONCLUSIONS: HDL-associated lysosphingolipids inhibit 
      NAD(P)H oxidase-dependent ROS generation and MCP-1 production in a process that 
      requires coordinate signaling through S1P(3) and SR-B1 receptors.
FAU - Tolle, Markus
AU  - Tolle M
AD  - Charite - Campus Benjamin Franklin, Medizinische Klinik, Berlin, Germany.
FAU - Pawlak, Alicja
AU  - Pawlak A
FAU - Schuchardt, Miriam
AU  - Schuchardt M
FAU - Kawamura, Akira
AU  - Kawamura A
FAU - Tietge, Uwe J
AU  - Tietge UJ
FAU - Lorkowski, Stefan
AU  - Lorkowski S
FAU - Keul, Petra
AU  - Keul P
FAU - Assmann, Gerd
AU  - Assmann G
FAU - Chun, Jerold
AU  - Chun J
FAU - Levkau, Bodo
AU  - Levkau B
FAU - van der Giet, Markus
AU  - van der Giet M
FAU - Nofer, Jerzy-Roch
AU  - Nofer JR
LA  - eng
GR  - R01 NS048478-05/NS/NINDS NIH HHS/United States
GR  - DA019674/DA/NIDA NIH HHS/United States
GR  - R01 DA019674-01A1/DA/NIDA NIH HHS/United States
GR  - R01 NS048478/NS/NINDS NIH HHS/United States
GR  - R01 NS048478-03/NS/NINDS NIH HHS/United States
GR  - R01 DA019674-03S1/DA/NIDA NIH HHS/United States
GR  - R01 DA019674-02/DA/NIDA NIH HHS/United States
GR  - NS048478/NS/NINDS NIH HHS/United States
GR  - R01 NS048478-02S1/NS/NINDS NIH HHS/United States
GR  - R01 NS048478-04/NS/NINDS NIH HHS/United States
GR  - R01 DA019674-04/DA/NIDA NIH HHS/United States
GR  - R01 DA019674/DA/NIDA NIH HHS/United States
GR  - R01 NS048478-02/NS/NINDS NIH HHS/United States
GR  - R01 DA019674-03/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080515
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Lysophospholipids)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Lysosphingolipid)
RN  - 0 (S1pr3 protein, mouse)
RN  - 0 (Scarb1 protein, mouse)
RN  - 0 (Scarb1 protein, rat)
RN  - 0 (Scavenger Receptors, Class B)
RN  - 0 (Sphingolipids)
RN  - 0 (Sphingosine-1-Phosphate Receptors)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*metabolism
MH  - Lipoproteins, HDL/physiology
MH  - Lysophospholipids/physiology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Smooth, Vascular/cytology/metabolism
MH  - Myocytes, Smooth Muscle/*metabolism
MH  - NADPH Oxidases/physiology
MH  - Rats
MH  - Rats, Inbred WKY
MH  - Reactive Oxygen Species/*metabolism
MH  - Receptors, Lysosphingolipid/physiology
MH  - Scavenger Receptors, Class B
MH  - Sphingolipids/chemistry/*physiology
MH  - Sphingosine/analogs & derivatives/physiology
MH  - Sphingosine-1-Phosphate Receptors
PMC - PMC2723752
MID - NIHMS125980
EDAT- 2008/05/17 09:00
MHDA- 2008/09/26 09:00
PMCR- 2009/08/10
CRDT- 2008/05/17 09:00
PHST- 2008/05/17 09:00 [pubmed]
PHST- 2008/09/26 09:00 [medline]
PHST- 2008/05/17 09:00 [entrez]
PHST- 2009/08/10 00:00 [pmc-release]
AID - ATVBAHA.107.161042 [pii]
AID - 10.1161/ATVBAHA.107.161042 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1542-8. doi: 
      10.1161/ATVBAHA.107.161042. Epub 2008 May 15.