Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL-1-Mediated Mechanism.
Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL-1-Mediated Mechanism.
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DOI：
10.1161/jaha.118.008757
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发表时间：
2018-06-30
影响因子：
5.4
通讯作者：
Francis SE
中科院分区：
文献类型：
--
作者：
Alfaidi MA;Chamberlain J;Rothman A;Crossman D;Villa-Uriol MC;Hadoke P;Wu J;Schenkel T;Evans PC;Francis SE
高血压是一种复杂的疾病，也是常见的心血管危险因素。饮食中的二十二碳六烯酸(DHA)可能通过炎症机制调节动脉粥样硬化和高血压。IL-1(IL-1)在动脉粥样硬化和炎症中的作用已经确立，尽管IL-1抑制是否调节血压尚不清楚。雄性载脂蛋白E−/−(载脂蛋白E缺失)小鼠喂饲高脂饲料或高脂饲料加DHA(300 mg/kg/d)，共12周。测定血压和心功能，并测定DHA对室壁切应力和动脉粥样硬化的影响。补充DHA改善了左心功能，降低了降主动脉开口处的室壁切应力和振荡切应力，并显著降低了血压(119.5±7 mm·Hg，P<；0.001，n=4)。对小鼠喂食DHA后的动脉粥样硬化的分析表明，动脉远端和头臂动脉的病变负担减少了4倍(P<；0.001，每组12例)。此外，DHA治疗选择性降低斑块内皮细胞IL-1β(P<；0.01)。我们的发现表明，通过在饮食中给予DHA间接抑制IL-1，可以降低血压升高，其机制涉及降低壁切应力和促炎细胞因子IL-1β的局部表达。
Hypertension is a complex condition and a common cardiovascular risk factor. Dietary docosahexaenoic acid (DHA) modulates atherosclerosis and hypertension, possibly via an inflammatory mechanism. IL‐1 (interleukin 1) has an established role in atherosclerosis and inflammation, although whether IL‐1 inhibition modulates blood pressure is unclear. Male apoE−/− (apolipoprotein E–null) mice were fed either a high fat diet or a high fat diet plus DHA (300 mg/kg per day) for 12 weeks. Blood pressure and cardiac function were assessed, and effects of DHA on wall shear stress and atherosclerosis were determined. DHA supplementation improved left ventricular function, reduced wall shear stress and oscillatory shear at ostia in the descending aorta, and significantly lowered blood pressure compared with controls (119.5±7 versus 159.7±3 mm Hg, P<0.001, n=4 per group). Analysis of atheroma following DHA feeding in mice demonstrated a 4‐fold reduction in lesion burden in distal aortas and in brachiocephalic arteries (P<0.001, n=12 per group). In addition, DHA treatment selectively decreased plaque endothelial IL‐1β (P<0.01). Our findings revealed that raised blood pressure can be reduced by inhibiting IL‐1 indirectly by administration of DHA in the diet through a mechanism that involves a reduction in wall shear stress and local expression of the proinflammatory cytokine IL‐1β.