Inhibition of NADPH oxidase by apocynin attenuates progression of atherosclerosis.
Inhibition of NADPH oxidase by apocynin attenuates progression of atherosclerosis.
复制标题
DOI：
10.3390/ijms140817017
复制
发表时间：
2013-08-19
影响因子：
5.6
通讯作者：
Miller FJ
中科院分区：
文献类型：
--
作者：
Kinkade K;Streeter J;Miller FJ
在血管中活性氧（ROS）的多种来源中，NADPH氧化酶是主要来源。尽管一些研究已经暗示NADPH氧化酶在动脉粥样硬化的起始中，但它们在疾病进展中的作用尚不完全清楚。我们的目的是确定抑制NADPH氧化酶在动脉粥样硬化中的潜在临床意义。使用动脉粥样硬化的高脂血症小鼠模型（正常饮食的ApoE−/−/LDLR−/−（AS）小鼠），我们首先建立了AS小鼠中超氧化物水平与病变大小之间的时间依赖性关系。接下来，我们确定NADPH氧化酶是动脉粥样硬化病变中ROS的主要来源。夹竹桃麻素通过阻止亚基p47 phox的转位而部分干扰NADPH氧化酶的活化，用AS小鼠的主动脉段治疗，显著降低了超氧化物水平。此外，除了夹竹桃麻素的AS小鼠的饮用水中产生的病变大小的减少相比，未经处理的AS小鼠，在胸腹主动脉的效果最明显，但没有从主动脉弓。AS+夹竹桃麻素小鼠的粒细胞功能被抑制，证实夹竹桃麻素治疗的疗效。我们得出结论，夹竹桃麻素减弱高胆固醇血症小鼠动脉粥样硬化的进展，可能是通过其抑制NADPH氧化酶产生超氧化物的能力。
Of the multiple sources of reactive oxygen species (ROS) in the blood vessel, NADPH oxidases are the primary source. Whereas several studies have implicated NADPH oxidases in the initiation of atherosclerosis, their roles in disease progression are incompletely understood. Our objective was to determine the potential clinical relevance of inhibiting NADPH oxidase in established atherosclerosis. Using a hypercholesteremic murine model of atherosclerosis (ApoE−/−/LDLR−/− (AS) mice on normal chow diet), we first established a time-dependent relationship between superoxide levels and lesion size in AS mice. Next, we identified NADPH oxidase as the primary source of ROS in atherosclerotic lesions. Treatment of aortic segments from AS mice with apocynin, which interferes with NADPH oxidase activation in part by preventing translocation of the subunit p47phox, significantly reduced superoxide levels. Moreover, addition of apocynin to the drinking water of AS mice produced a decrease in lesion size as compared to untreated AS mice, with the effect most pronounced in the thoracoabdominal aorta but absent from the aortic arch. Granulocyte function in AS+apocynin mice was suppressed, confirming efficacy of apocynin treatment. We conclude that apocynin attenuates the progression of atherosclerosis in hypercholesterolemic mice, potentially by its ability to inhibit generation of superoxide by NADPH oxidase.
登录
查看更多内容
影响因子：
7.4
作者：
Barbieri, SS;Cavalca, V;Colli, S
通讯作者：
Colli, S
影响因子：
37.8
作者：
Thomas, Manesh;Gavrila, Dan;Weintraub, Neal L.
通讯作者：
Weintraub, Neal L.
影响因子：
20.1
作者：
Hathaway, CA;Heistad, DD;Miller, FJ
通讯作者：
Miller, FJ
影响因子：
15.9
作者：
Barry-Lane, PA;Patterson, C;Runge, MS
通讯作者：
Runge, MS
影响因子：
120.1
作者：
Drummond, Grant R.;Selemidis, Stavros;Griendling, Kathy K.;Sobey, Christopher G.
通讯作者：
Sobey, Christopher G.