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Atherogenic properties of LDL particles modified by human group X secreted phospholipase A2 on human endothelial cell function
Author(s) -
Karabina SoniaAthina,
Brochériou Isabelle,
Le Naour Gilles,
Agrapart Monique,
Durand Hervé,
Gelb Michael,
Lambeau Gérard,
Ninio Ewa
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-6018fje
Subject(s) - phospholipase a2 , arachidonic acid , phospholipid , biochemistry , lipid signaling , lipoprotein , phospholipase , proinflammatory cytokine , endothelial stem cell , lipoprotein associated phospholipase a2 , chemistry , lysophosphatidylcholine , foam cell , low density lipoprotein , cell adhesion molecule , enzyme , microbiology and biotechnology , inflammation , biology , phosphatidylcholine , in vitro , cholesterol , membrane , immunology
Increasing evidence suggests that se‐creted phospholipases A2 (sPLA2s) play an important role in the pathophysiology of atherosclerosis. Among sPLA2s, the human group X (hGX) enzyme has the highest catalytic activity toward phosphatidylcholine, one of the major phospholipid species of cell mem‐ branes and low‐density lipoprotein (LDL). Our study examined the presence of hGX sPLA2 in human atherosclerotic lesions and investigated the ability of hGX modified LDL to alter human endothelial cell (HUVEC) function. Our results show that hGX sPLA2 is present in human atherosclerotic lesions and that the hydrolysis of LDL by hGX sPLA2 results in a modified particle that induces lipid accumulation in human monocyte‐derived macrophages. Acting on endothelial cells, hGX‐modified LDL activates the MAP kinase pathway, which leads to increased arachidonic acid release, increased expression of adhesion molecules on the surface of HUVEC, and increased adhesion of monocytes to HUVEC monolayers. Together, our data suggest that LDL modified by hGX, rather than hGX itself may have strong proinflammatory and proatherogenic properties, which could play an important role in the propagation of atherosclerosis.—Karabina, S. A., Brocheriou, I., Le Naour, G., Agrapart, M., Durand, H., Gelb, M., Lambeau, G., Ninio, E. Atherogenic properties of LDL particles modified by human group X secreted phospholipase A2 on human endothelial cell function. FASEB J. 20, E1890–E1900 (2006)