Rosengren Birgitta, Jönsson-Rylander Ann-Cathrine, Peilot Helena, Camejo German, Hurt-Camejo Eva
AstraZeneca, R&D, Molecular Pharmacology, Mölndal S-431 83, Sweden.
Biochim Biophys Acta. 2006 Nov;1761(11):1301-8. doi: 10.1016/j.bbalip.2006.06.008. Epub 2006 Jul 8.
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.
临床观察有力地支持了分泌型磷脂酶A2（sPLA(2)）循环水平与动脉粥样硬化性心血管疾病（ACVD）之间的关联。两种作用模式可为这些统计相关性提供因果支持。一种是酶对循环脂蛋白的作用，另一种是对一旦进入动脉细胞外内膜的脂蛋白的直接作用。在本综述中，我们讨论了一些结果，这些结果表明，sPLA(2)-IIA和sPLA(2)-V在定位、对血浆脂蛋白的作用以及与动脉蛋白聚糖的相互作用方面具有不同的特征。观察到的差异表明，这些酶可能通过不同途径促成动脉粥样硬化。此外，我们对我们实验室最近的动物研究进行了评论，这些研究表明，V型酶的表达在遗传和营养诱导的血脂异常中上调，但IIA型酶则不然，众所周知，IIA型酶在急性炎症中上调。结果表明，如果人类因高脂血症而出现类似的上调，可能会在V型酶与疾病之间建立独特的联系。
