Rosengren Birgitta, Peilot Helena, Umaerus Mia, Jönsson-Rylander Ann-Cathrine, Mattsson-Hultén Lillemor, Hallberg Carina, Cronet Philippe, Rodriguez-Lee Mariam, Hurt-Camejo Eva
AstraZeneca, R&D, Molecular Pharmacology, Mölndal S-431 83, Sweden.
Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1579-85. doi: 10.1161/01.ATV.0000221231.56617.67. Epub 2006 Apr 6.
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.
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.
These results indicate that these phospholipases could have different roles in atherosclerosis.
研究V型分泌型磷脂酶A2（sPLA2）在人和小鼠病变中的分布，并比较其在人血管细胞中的表达、对脂蛋白的活性以及与动脉蛋白聚糖的相互作用与sPLA2-IIA的异同。此外，我们还研究了西方饮食和脂多糖刺激对小鼠模型主动脉中这些酶表达的影响。
免疫组织化学显示，人和小鼠病变中的sPLA2-V与平滑肌细胞以及脂质核心区域周围的泡沫细胞相关。该酶的mRNA在人病变组织和人血管细胞中表达，支持了免疫组织化学数据。sPLA2-V而非sPLA2-IIA对人血清中的脂蛋白有活性。与蛋白聚糖的结合使sPLA2-V对低密度脂蛋白的活性增强2至3倍，但对IIA型酶无此作用。小鼠模型实验表明，西方饮食处理可诱导主动脉中sPLA2-V的表达，但不能诱导sPLA2-IIA的表达。另一方面，脂多糖诱导的急性炎症增强了sPLA2-IIA的表达，但未增强sPLA2-V的表达。
这些结果表明，这些磷脂酶在动脉粥样硬化中可能具有不同作用。
