Xuezhikang, an extract from red yeast rice, attenuates vulnerable plaque progression by suppressing endoplasmic reticulum stress-mediated apoptosis and inflammation.
Xuezhikang, an extract from red yeast rice, attenuates vulnerable plaque progression by suppressing endoplasmic reticulum stress-mediated apoptosis and inflammation.
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血脂康是一种红曲米提取物，通过抑制内质网应激介导的细胞凋亡和炎症来减轻易损斑块的进展
DOI：
10.1371/journal.pone.0188841
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
He B
中科院分区：
文献类型：
--
作者：
Shen L;Sun Z;Chu S;Cai Z;Nie P;Wu C;Yuan R;Hu L;He B
血脂康（XZK）是红曲米的提取物，是一种在中国和其他国家广泛用于治疗心血管疾病的中药。然而，XZK治疗是否可以改善动脉粥样硬化斑块的稳定性尚不完全清楚。基于我们之前开发的 ApoE-/- 小鼠颈动脉自发易损斑块形成和破裂的小鼠模型。我们发现，低剂量（600 mg/kg/d）XZK 在不减少斑块面积的情况下改善了斑块稳定性，而高剂量（1200 mg/kg/d）XZK 显着抑制了易损斑块的进展，同时减少了斑块面积。从机制上讲，XZK 显着抑制小鼠颈动脉病变内质网 (ER) 应激。在体外，XZK 抑制 RAW264.7 巨噬细胞中 7-KC 诱导的 ER 应激激活，通过降低 p-PERK、p-IRE1α、p-eIF2α、c-ATF6、s-XBP1 和 CHOP 水平进行评估。与对照组相比，XZK治疗组的凋亡细胞数量显着减少（表现为TUNEL阳性细胞和裂解的caspase3阳性细胞减少）、坏死核心面积和比例降低以及NF-κB靶基因表达降低。在 RAW264.7 细胞中，XZK 抑制 7-KC 诱导的细胞凋亡上调、细胞凋亡标记物（裂解的 caspase-3 和裂解的 PARP）的蛋白表达以及 NF-κB 激活（通过靶基因转录和 IκBα 减少显示）。总的来说，我们的结果表明，XZK 通过减轻巨噬细胞 ER 应激，从而抑制细胞凋亡和 NF-κB 促炎途径，有效抑制易损斑块进展和破裂，从而为稳定动脉粥样硬化斑块提供替代治疗策略。
Xuezhikang (XZK), an extract of red yeast rice, is a traditional Chinese medicine widely used for the treatment of cardiovascular diseases in China and other countries. However, whether XZK treatment can improve atherosclerotic plaque stability is not fully understood. Based on our previously developed mouse model of spontaneous vulnerable plaque formation and rupture in carotid arteries in ApoE-/- mice. We showed that low-dose (600 mg/kg/d) XZK improved plaque stability without decreasing plaque area, whereas high-dose (1200 mg/kg/d) XZK dramatically inhibited vulnerable plaque progression accompanied by decreased plaque area. Mechanistically, XZK significantly suppressed lesional endoplasmic reticulum (ER) stress in mouse carotid arteries. In vitro, XZK inhibited 7-KC-induced activation of ER stress in RAW264.7 macrophages, as assessed by the reduced levels of p-PERK, p-IRE1α, p-eIF2α, c-ATF6, s-XBP1, and CHOP. Compared to controls, the XZK-treated group displayed dramatically decreased apoptotic cell numbers (shown by decreased TUNEL- and cleaved caspase3-positive cells), lower necrotic core area and ratio, and reduced expression of NF-κB target gene. In RAW264.7 cells, XZK inhibited 7-KC-induced upregulation of apoptosis, protein expression of apoptotic markers (cleaved caspase-3 and cleaved PARP), and NF-κB activation (shown by target gene transcription and IκBα reduction). Collectively, our results suggest that XZK effectively suppresses vulnerable plaque progression and rupture by mitigating macrophage ER stress and consequently inhibiting apoptosis and the NF-κB pro-inflammatory pathway, thereby providing an alternative therapeutic strategy for stabilizing atherosclerotic plaques.
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影响因子：
11.2
作者：
Liu J;Zhou W;Li SS;Sun Z;Lin B;Lang YY;He JY;Cao X;Yan T;Wang L;Lu J;Han YH;Cao Y;Zhang XK;Zeng JZ
通讯作者：
Zeng JZ
影响因子：
82.9
作者：
Erbay, Ebru;Babaev, Vladimir R.;Mayers, Jared R.;Makowski, Liza;Charles, Khanichi N.;Snitow, Melinda E.;Fazio, Sergio;Wiest, Michelle M.;Watkins, Steven M.;Linton, MacRae F.;Hotamisligil, Goekhan S.
通讯作者：
Hotamisligil, Goekhan S.
DOI：
10.1253/circj.cj-16-0924
发表时间：
2016-10-25
期刊：
Circulation journal : official journal of the Japanese Circulation Society
影响因子：
--
作者：
Linton MF;Babaev VR;Huang J;Linton EF;Tao H;Yancey PG
通讯作者：
Yancey PG
影响因子：
5
作者：
Li, JJ;Hu, SS;Gao, RL
通讯作者：
Gao, RL
DOI：
10.1161/01.atv.0000189159.96900.d9
发表时间：
2005-12-01
影响因子：
8.7
作者：
Dickhout, JG;Hossain, GS;Austin, RC
通讯作者：
Austin, RC