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. METHODS AND 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.

Nyckelord

Animals

Antigens

CD14/analysis

Aorta/*enzymology

Arteries/*metabolism

Atherosclerosis/*enzymology/*pathology

Blood/drug effects

Blood Vessels/enzymology/pathology

Carotid Artery Diseases/enzymology/pathology

*Diet

Drug Interactions

Enzyme Induction

Humans

Immunohistochemistry/methods

Isoenzymes/genetics/metabolism/pharmacology

Lipoproteins/drug effects

Macrophages/enzymology/immunology

Mice

Phospholipases A/genetics/*metabolism/pharmacology

Proteoglycans/*metabolism

RNA

Messenger/metabolism

Recombinant Proteins/pharmacology

Staining and Labeling

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)