HDL-Associated Lysosphingolipids Inhibit NAD(P)H Oxidase-Dependent Monocyte Chemoattractant Protein-1 Production

Autor: Alicja Pawlak, Jerold Chun, Markus van der Giet, Akira Kawamura, Stefan Lorkowski, Bodo Levkau, Gerd Assmann, Markus Tölle, Jerzy-Roch Nofer, Uwe J. F. Tietge, M. Schuchardt, Petra Keul
Přispěvatelé: Center for Liver, Digestive and Metabolic Diseases (CLDM), Lifestyle Medicine (LM)
Rok vydání: 2008
Předmět:
Male
Vascular smooth muscle
SMOOTH-MUSCLE-CELLS
Rats
Inbred WKY
Muscle
Smooth
Vascular
Mice
chemistry.chemical_compound
Sphingosine
NADPH OXIDASE
Receptor
Chemokine CCL2
Mice
Knockout
NADPH oxidase
ROS
Scavenger Receptors
Class B
Receptors
Lysosphingolipid
Biochemistry
NAD(P)H oxidase
lipids (amino acids
peptides
and proteins)
Lipoproteins
HDL
Cardiology and Cardiovascular Medicine
NADPH-oxidase
EXPRESSION
medicine.medical_specialty
OXIDIZED LDL
HDL
Myocytes
Smooth Muscle
E-SELECTIN
Biology
Article
INFLAMMATION
Internal medicine
medicine
Animals
Sphingosine-1-phosphate
Sphingosine-1-Phosphate Receptors
Sphingolipids
SPHINGOSINE-1-PHOSPHATE
NADPH Oxidases
ENDOTHELIAL-CELLS
Rats
Endocrinology
ATHEROSCLEROSIS
chemistry
biology.protein
NAD+ kinase
Lysophospholipids
Reactive Oxygen Species
MCP-1
APOE(-/-) MICE
Lipoprotein
Zdroj: Arteriosclerosis thrombosis and vascular biology, 28(8), 1542-1548. LIPPINCOTT WILLIAMS & WILKINS
ISSN: 1524-4636
1079-5642
DOI: 10.1161/atvbaha.107.161042
Popis: Objectives— 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. Conclusion— 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.
Databáze: OpenAIRE
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