Secretory phospholipase A2 group V: lesion distribution, activation by arterial proteoglycans, and induction in aorta by a Western diet.
OBJECTIVE
To study the distribution of group V secretory phospholipase A2 (sPLA2) in human and mouse lesions and compare its expression by human vascular cells, its activity toward lipoproteins, and the interaction with arterial proteoglycans (proteoglycans) with those of sPLA2-IIA. In addition, we also investigated the effect of a Western diet and lipopolysaccharide challenge on the aortic expression of these enzymes in mouse models.


RESULTS
Immunohistochemistry showed sPLA2-V in human and mouse lesions to be associated with smooth muscle cells and also surrounding foam cells in lipid core areas. mRNA of the enzyme was expressed in human lesions and human vascular cells, supporting the immunohistochemistry data. sPLA2-V but not sPLA2-IIA was active on lipoproteins in human serum. The association with proteoglycans enhanced 2- to 3-fold sPLA2-V activity toward low-density lipoproteins but not that of the group IIA enzyme. Experiments in mouse models showed that treatment with a Western diet induced expression of sPLA2-V but not that of sPLA2-IIA in aorta. On the other hand, lipopolysaccharide-induced acute inflammation augmented the expression of sPLA2-IIA but not that of sPLA2-V.


CONCLUSIONS
These results indicate that these phospholipases could have different roles in atherosclerosis.
Rosengren
Birgitta
B
AstraZeneca, R&D, Molecular Pharmacology, Mölndal S-431 83, Sweden.
Peilot
Helena
H
Umaerus
Mia
M
Jönsson-Rylander
Ann-Cathrine
AC
Mattsson-Hultén
Lillemor
L
Hallberg
Carina
C
Cronet
Philippe
P
Rodriguez-Lee
Mariam
M
Hurt-Camejo
Eva
E
D000818:Animals; D001011:Aorta / Q000201:enzymology*; D001158:Arteries / Q000378:metabolism*; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology*; D001769:Blood / Q000187:drug effects; D001808:Blood Vessels / Q000201:enzymology / Q000473:pathology; D002340:Carotid Artery Diseases / Q000201:enzymology / Q000473:pathology; D004032:Diet; D004347:Drug Interactions; D004790:Enzyme Induction; D054501:Group II Phospholipases A2; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008074:Lipoproteins / Q000187:drug effects; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D051379:Mice; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D054467:Phospholipases A2; D011509:Proteoglycans / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013194:Staining and Labeling
D007527:Isoenzymes; D018950:Lipopolysaccharide Receptors; D008074:Lipoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2