Apoptosis signal-regulating kinase 1 deficiency eliminates cardiovascular injuries induced by high-salt diet
Apoptosis signal-regulating kinase 1 deficiency eliminates cardiovascular injuries induced by high-salt diet
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DOI：
10.1097/hjh.0b013e32833fc8b0
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发表时间：
2011-01-01
影响因子：
4.9
通讯作者：
Kim-Mitsuyama, Shokei
中科院分区：
文献类型：
--
作者：
Kataoka, Keiichiro;Tokutomi, Yoshiko;Kim-Mitsuyama, Shokei
目的高盐饮食与心血管事件的增加密切相关。然而，高盐致心血管损伤的机制尚不清楚。方法对野生型和ASK1-/-小鼠分别给予低盐和高盐饮食10周，比较高盐饮食对两组小鼠摄食量、尿量和电解质排泄以及心血管损伤的影响。结果高盐饮食使野生型和ASK1-/-S小鼠的摄食量、饮水量、尿量和尿钠排泄量增加，血浆肾素活性和醛固酮水平降低。因此，ASK1似乎在高盐饮食引起的钠尿增加和血浆肾素和醛固酮下降中起到了次要作用。高盐饮食可增强野生型小鼠心血管ASK1的磷酸化。野生型小鼠的高盐饮食增加了心脏转化生长因子-β1、间质纤维化、冠状动脉血管周围纤维化和炎症细胞浸润，这些变化与心脏超氧化物和NOX2的增加有关。ASK1缺乏可消除上述高盐所致的心脏损伤。高盐饮食对乙酰胆碱所致的血管内皮依赖性舒张功能也有一定的损伤作用，使野生型小鼠的血管内皮细胞超氧化物歧化和一氧化氮合酶水平升高，而对ASK1/-S小鼠则无明显影响。结论Ask1基因可能通过增强氧化应激而参与心脏炎症和纤维化以及高盐饮食所致的血管内皮功能障碍。J Hyperten 29：76-84(C)2010 Wolters Kluwer Health|Lippincott Williams&Wilkins.
Objectives High-salt diet is closely associated with the increase in cardiovascular events. However, the mechanism of high-salt-induced cardiovascular injury is unknown. The present study was undertaken to test our hypothesis that apoptosis signal-regulating kinase (ASK) 1 may be involved in salt-induced cardiovascular injury.Methods Wild-type and ASK1-/- mice were fed a low-salt or a high-salt diet for 10 weeks and the effects of high-salt diet on food intake, urinary volume and electrolyte excretion, and cardiovascular injury were compared between both groups of mice.Results High-salt diet in wild-type and ASK1-/- S mice similarly increased food intake, water intake, urine volume, and urinary sodium excretion, and comparably decreased plasma renin activity and aldosterone. Thus, ASK1 appears to play a minor role in the increase in natriuresis and the decrease in plasma renin, and aldosterone caused by high-salt diet. High-salt diet enhanced the phosphorylation of cardiovascular ASK1 in wild-type mice. High-salt diet in wild-type mice enhanced cardiac transforming growth factor-beta 1, interstitial fibrosis, coronary perivascular fibrosis, and inflammatory cell infiltration, and these changes were associated with the increase in cardiac superoxide and Nox2. ASK1 deficiency abolished the above-mentioned high-salt-induced cardiac injury. High-salt diet also caused the impairment of vascular endothelium-dependent relaxation by acetylcholine and increased vascular superoxide, and Nox2 in wild-type mice, whereas it did not cause vascular injury in ASK1-/- S mice.Conclusion ASK1 is implicated in cardiac inflammation and fibrosis, and vascular endothelial dysfunction caused by high-salt diet, through the enhancement of oxidative stress. J Hypertens 29:76-84 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.