Atherogenic properties of LDL particles modified by human group X secreted phospholipase A2 on human endothelial cell function.
Increasing evidence suggests that secreted 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 membranes 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
Sonia-Athina
SA
INSERM UMRS 525, Faculté de Médecine Pierre et Marie Curie, 91, boulevard de l'Hôpital, 75634 Paris, France. akarampi@chups.jussieu.fr
Brochériou
Isabelle
I
Le Naour
Gilles
G
Agrapart
Monique
M
Durand
Hervé
H
Gelb
Michael
M
Lambeau
Gérard
G
Ninio
Ewa
E
D001158:Arteries / Q000166:cytology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D008078:Cholesterol, LDL / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D054509:Group X Phospholipases A2; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D014680:Veins / Q000166:cytology
D015815:Cell Adhesion Molecules; D008078:Cholesterol, LDL; D012333:RNA, Messenger; D010741:Phospholipases A; D054509:Group X Phospholipases A2; C516365:PLA2G10 protein, human; D054467:Phospholipases A2