Distinctiveness of secretory phospholipase A2 group IIA and V suggesting unique roles in atherosclerosis.
Clinical observations strongly support an association of circulating levels of secretory phospholipases A(2) (sPLA(2)) in atherosclerotic cardiovascular disease (ACVD). Two modes of action can provide causal support for these statistical correlations. One is the action of the enzymes on circulating lipoproteins and the other is direct action on the lipoproteins once in the arterial extracellular intima. In this review we discuss results suggesting a distinct profile of characteristics related to localization, action on plasma lipoproteins and interaction with arterial proteoglycans for sPLA(2)-IIA and sPLA(2)-V. The differences observed indicate that these enzymes may contribute to atherosclerosis through dissimilar pathways. Furthermore, we comment on recent animal studies from our laboratory indicating that the expression of type V enzyme is up-regulated by genetically and nutritionally-induced dyslipidemias but not the group type IIA enzyme, which is well known to be up-regulated by acute inflammation. The results suggest that if similar up-regulation occurs in humans in response to hyperlipidemia, it may create a distinctive link between the group V enzyme and the disease.
Rosengren
Birgitta
B
AstraZeneca, R&D, Molecular Pharmacology, Mölndal S-431 83, Sweden.
Jönsson-Rylander
Ann-Cathrine
AC
Peilot
Helena
H
Camejo
German
G
Hurt-Camejo
Eva
E
D000208:Acute Disease; D000818:Animals; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D054501:Group II Phospholipases A2; D054505:Group V Phospholipases A2; D006801:Humans; D006949:Hyperlipidemias / Q000201:enzymology / Q000473:pathology; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D008074:Lipoproteins / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011509:Proteoglycans / Q000378:metabolism; D017539:Tunica Intima / Q000201:enzymology / Q000473:pathology; D015854:Up-Regulation
D008074:Lipoproteins; D011509:Proteoglycans; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054505:Group V Phospholipases A2; C516299:PLA2G5 protein, human; D054467:Phospholipases A2