Group V secreted phospholipase A2 plays a protective role against aortic dissection
Group V secreted phospholipase A2 plays a protective role against aortic dissection
复制标题
DOI：
10.1074/jbc.ra120.013753
复制
发表时间：
2020-07-24
影响因子：
4.8
通讯作者：
Murakami, Makoto
中科院分区：
文献类型：
--
作者：
Watanabe, Kazuhiro;Taketomi, Yoshitaka;Murakami, Makoto
主动脉夹层是一种危及生命的血管病，涉及主动脉壁分离，其潜在机制仍不完全清楚。流行病学证据表明，不饱和脂肪酸改善心血管健康。在这里，我们使用定量RT-PCR，组织学分析，磁细胞分选和流式细胞术测定，和MS为基础的脂质组学，我们表明，活性的脂质代谢酶，分泌型磷脂酶A（2）V组（sPLA（2）-V），防止主动脉夹层通过内源性动员血管保护脂质。整体和内皮细胞特异性sPLA（2）-V缺陷小鼠经常在血管紧张素II（AT-II）输注后不久发生主动脉夹层。我们观察到，在AT-II处理的主动脉中，内皮sPLA（2）-V动员油酸和亚油酸，这减弱了内质网应激，增加了赖氨酰氧化酶的表达，从而稳定了主动脉中的细胞外基质。值得注意的是，饮食中补充油酸或亚油酸可以逆转sPLA（2）-V缺陷小鼠对主动脉夹层的易感性增加。这些发现揭示了sPLA（2）驱动的磷脂代谢与主动脉稳定性之间未探索的功能联系，可能有助于开发预防主动脉夹层的改进诊断和/或治疗策略。
Aortic dissection is a life-threatening aortopathy involving separation of the aortic wall, whose underlying mechanisms are still incompletely understood. Epidemiological evidence suggests that unsaturated fatty acids improve cardiovascular health. Here, using quantitative RT-PCR, histological analyses, magnetic cell sorting and flow cytometry assays, and MS-based lipidomics, we show that the activity of a lipid-metabolizing enzyme, secreted phospholipase A(2) group V (sPLA(2)-V), protects against aortic dissection by endogenously mobilizing vasoprotective lipids. Global and endothelial cell-specific sPLA(2)-V-deficient mice frequently developed aortic dissection shortly after infusion of angiotensin II (AT-II). We observed that in the AT-II-treated aorta, endothelial sPLA(2)-V mobilized oleic and linoleic acids, which attenuated endoplasmic reticulum stress, increased the expression of lysyl oxidase, and thereby stabilized the extracellular matrix in the aorta. Of note, dietary supplementation with oleic or linoleic acid reversed the increased susceptibility of sPLA(2)-V-deficient mice to aortic dissection. These findings reveal an unexplored functional link between sPLA(2)-driven phospholipid metabolism and aortic stability, possibly contributing to the development of improved diagnostic and/or therapeutic strategies for preventing aortic dissection.