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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1579.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Secretory Phospholipase A₂ Group V

Lesion Distribution, Activation by Arterial Proteoglycans, and Induction in Aorta by a Western Diet

Birgitta Rosengren; Helena Peilot; Mia Umaerus; Ann-Cathrine Jönsson-Rylander; Lillemor Mattsson-Hultén; Carina Hallberg; Philippe Cronet; Mariam Rodriguez-Lee; Eva Hurt-Camejo

From AstraZeneca (B.R., M.U., A.-C.J.-R., C.H., P.C., E.H.-C.), R&D, Molecular Pharmacology, Mölndal, Sweden; and Wallenberg Laboratory (H.P., L.M.-H., M.R.-L., E.H.-C.), Sahlgrenska University Hospital, Göteborg, Sweden.

Correspondence to Eva Hurt-Camejo, AstraZeneca, R&D, Molecular Pharmacology, Mölndal S-431 83, Sweden. E-mail eva.hurt-camejo{at}astrazeneca.com

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.

SPLA₂-V was observed in human and mouse lesions associated with smooth muscle cells and surrounding foam cells in lipid cores. Proteoglycans increased the activity of sPLA₂-V toward low-density lipoproteins. Western diet induced sPLA₂-V expression in mouse aorta but not that of sPLA₂-IIA. These enzymes may contribute to atherosclerosis by different pathways.

Key Words: phospholipase • atherogenesis • inflammation • lipoprotein-retention • proteoglycans

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Frederick C. de Beer and Nancy R. Webb
Arterioscler Thromb Vasc Biol 2006 26: 1421-1422. [Extract] [Full Text] [PDF]

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