Free Fatty Acid Causes Leukocyte Activation and Resultant Endothelial Dysfunction Through Enhanced Angiotensin II Production in Mononuclear and Polymorphonuclear Cells
Free Fatty Acid Causes Leukocyte Activation and Resultant Endothelial Dysfunction Through Enhanced Angiotensin II Production in Mononuclear and Polymorphonuclear Cells
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DOI：
10.1161/hypertensionaha.110.153056
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发表时间：
2010-07-01
期刊：
影响因子：
8.3
通讯作者：
Ueda, Shinichiro
中科院分区：
文献类型：
--
作者：
Azekoshi, Yoko;Yasu, Takanori;Ueda, Shinichiro
脂肪组织中游离脂肪酸（FFA）的释放与内脏脂肪肥胖患者的胰岛素抵抗和内皮功能障碍有关。我们之前证明，FFA 水平升高会导致内皮功能障碍，而通过抑制人类肾素-血管紧张素系统 (RAS) 可以防止内皮功能障碍。然而，FFA 介导的 RAS 激活和由此产生的内皮功能障碍的机制尚未阐明。我们研究了升高的 FFA 对循环和血管 RAS 活性、白细胞血管紧张素 II 形成活性以及血压正常受试者白细胞活化的影响。我们发现，FFA 水平的增加显着增强了人单核细胞（平均倍数增加：180 分钟时增加 3.5 倍；P=0.0016）和多形核细胞（2.0；P=0.0012）的血管紧张素 II 形成活性，而循环和血管 RAS 参数不受影响。我们还表明，FFA 会引起血管紧张素 II 依赖性白细胞活化，部分通过增加髓过氧化物酶释放并可能增强白细胞粘附来损害内皮功能。我们认为 FFA 在单核和多形核细胞中增强血管紧张素 II 的产生，导致白细胞活化，从而损害内皮功能。白细胞中的 RAS 可能作为人类中的移动 RAS 来调节白细胞与血管的相互作用。 （高血压。2010；56：136-142。）
Release of free fatty acid (FFA) from adipose tissue is implicated in insulin resistance and endothelial dysfunction in patients with visceral fat obesity. We demonstrated previously that increased FFA levels cause endothelial dysfunction that is prevented by inhibition of the renin-angiotensin system (RAS) in humans. However, the mechanisms for FFA-mediated activation of RAS and the resultant endothelial dysfunction were not elucidated. We investigated effects of elevated FFA on activity of circulating and vascular RAS, angiotensin II-forming activity of leukocytes, and leukocyte activation of normotensive subjects. We showed that increased FFA levels significantly enhanced angiotensin II-forming activity in human mononuclear (mean fold increase: 3.5 at 180 minutes; P=0.0016) and polymorphonuclear (2.0; P=0.0012) cells, whereas parameters of the circulating and vascular RAS were not affected. We also showed that FFA caused angiotensin II-dependent leukocyte activation, which impaired endothelial function partly via increased myeloperoxidase release and presumably enhanced adhesion of leukocytes. We propose that the enhanced production of angiotensin II by FFA in mononuclear and polymorphonuclear cells causes activation of leukocytes that consequently impairs endothelial function. RAS in leukocytes may regulate the leukocyte-vasculature interaction as the mobile RAS in humans. (Hypertension. 2010; 56: 136-142.)