Association of aorta intima permeability with myosin light chain kinase expression in hypercholesterolemic rabbits

Association of aorta intima permeability with myosin light chain kinase expression in hypercholesterolemic rabbits
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高胆固醇血症兔主动脉内膜通透性与肌球蛋白轻链激酶表达的关系

DOI:
10.1007/s11010-010-0630-3
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发表时间:
2011-01-01
影响因子:
4.3
通讯作者:
Wang, Yuan
Wang, Yuan
中科院分区:
生物学3区
文献类型:
--
作者:
Zhu, Hua-Qing;Zhou, Qing;Wang, Yuan

文献摘要

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高胆固醇血症的发展是一个多因素的过程,其中血浆胆固醇水平升高起着核心作用。本研究分析了正常和高胆固醇饮食喂养后兔动脉壁肌球蛋白轻链激酶(MLCK)表达和活性以及内皮通透性的变化。通过高胆固醇饮食诱导高胆固醇血症4周。取出主动脉并分析内皮渗透性和MLCK表达。分析动脉中膜样品的MLCK活性和表达。用选择性MLCK抑制剂1-(5-碘萘-1-磺酰基)-1H-六氢-1,4-二氮杂卓盐酸盐(ML 7)治疗高胆固醇血症家兔(1 mg/kg体重)。高胆固醇饮食家兔的动脉显示MLCK表达和活性增加(与对照组相比增加近三倍)以及内皮通透性增加。ML 7抑制MLC磷酸化和MLCK活性(与对照相比几乎两倍)和由胆固醇刺激的内皮渗透性。这些结果首次表明,高胆固醇血症可能与MLCK表达和活性相关,通过MLCK表达和活性,内皮通透性增加。
The development of hypercholesterolemia is a multifactorial process in which elevated plasma cholesterol levels play a central role. This study analyzed the variability of the expression and activity of myosin light chain kinase (MLCK) and endothelial permeability in the artery wall of rabbits after feeding the animals with a normal or a high-cholesterol diet. Hypercholesterolemia was induced by a high-cholesterol diet for 4 weeks. Aortas were removed and analyzed for endothelial permeability and MLCK expression. Samples of the arterial media were analyzed for MLCK activity and expression. A selective MLCK inhibitor 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML7) were used in hypercholesterolemia rabbit (1 mg/kg body weight). The aortas of high-cholesterol diet rabbits showed an increase in MLCK expression and activity (nearly threefold compare with control) as well as endothelial permeability. ML7 inhibit MLC phosphorylation and MLCK activity (nearly twofold compare with control) and endothelial permeability stimulated by cholesterol. These results indicate for the first time that hypercholesterolemia may be associated with MLCK expression and activity through which endothelial permeability is increased.