GLP-1 Agonists Inhibit ox-LDL Uptake in Macrophages by Activating Protein Kinase A
GLP-1 Agonists Inhibit ox-LDL Uptake in Macrophages by Activating Protein Kinase A
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DOI：
10.1097/fjc.0000000000000087
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发表时间：
2014-07-01
影响因子：
3
通讯作者：
Mehta, Jawahar L.
中科院分区：
文献类型：
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作者：
Dai, Yao;Dai, Dongsheng;Mehta, Jawahar L.
氧化低密度脂蛋白（ox-LDL）的单核细胞/巨噬细胞的摄取在动脉粥样硬化的发生中起着关键作用。本研究旨在研究胰高血糖素样肽-1（GLP-1）激动剂对巨噬细胞摄取ox-LDL的影响。将人原代单核细胞/巨噬细胞与天然GLP-1（nGLP-1）或GLP-1激动剂利拉鲁肽一起孵育，以评价其在此过程中对ox-LDL摄取和清道夫受体（SR）（如SR-A、CD 36和凝集素样ox-LDL SR-1）表达的影响。我们的研究显示，nGLP-1或利拉鲁肽处理的巨噬细胞中ox-LDL摄取和CD 36表达降低。然而，nGLP-1和利拉鲁肽不影响其他SR SR-A和凝集素样ox-LDL SR-1的表达。同时，活化蛋白激酶A（PKA）的表达增加。为了检查PKA在nGLP-1或利拉鲁肽作用中的作用，我们用PK抑制剂（6-22）酰胺（一种PKA抑制剂）处理巨噬细胞，然后用nGLP-1或利拉鲁肽处理。抑制PKA活化可显著逆转nGLP-1或利拉鲁肽对ox-LDL摄取的影响，并增强CD 36的表达。我们的研究结果表明，GLP-1激动剂通过PKA/CD 36途径抑制巨噬细胞对ox-LDL的摄取。本研究为泡沫细胞形成机制和GLP-1激动剂在其中的作用提供了新的见解。
Oxidized low-density lipoprotein (ox-LDL) uptake by monocytes/macrophages plays a pivotal role in atherogenesis. This study was designed to examine the effect of glucagon-like peptide-1 (GLP-1) agonists on ox-LDL uptake in macrophages. Human primary monocytes/macrophages were incubated with native GLP-1 (nGLP-1) or GLP-1 agonist liraglutide to evaluate their effect on ox-LDL uptake and the expression of scavenger receptors (SRs), such as SR-A, CD36, and lectin-like ox-LDL SR-1, in this process. Our study showed a decrease in ox-LDL uptake and CD36 expression in macrophages treated with nGLP-1 or liraglutide. However, nGLP-1 and liraglutide did not affect the expression of other SRs SR-A and lectin-like ox-LDL SR-1. Simultaneously, there was an increase in the expression of activated protein kinase A (PKA). To examine the role of PKA in the effects of nGLP-1 or liraglutide, we treated macrophages with PK inhibitor (6-22) amide, a PKA inhibitor, followed by treatment with nGLP-1 or liraglutide. Inhibition of PKA activation markedly reversed the effect of nGLP-1 or liraglutide on ox-LDL uptake and enhanced the expression of CD36. Our results suggest that GLP-1 agonism inhibits ox-LDL uptake through PKA/CD36 pathway in macrophages. This study provides a novel insight in the mechanism of foam cell formation and the role by GLP-1 agonists therein.