Intermittent Fasting Inhibits High-Fat Diet-Induced Atherosclerosis by Ameliorating Hypercholesterolemia and Reducing Monocyte Chemoattraction.
Intermittent Fasting Inhibits High-Fat Diet-Induced Atherosclerosis by Ameliorating Hypercholesterolemia and Reducing Monocyte Chemoattraction.
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间歇性禁食通过改善高胆固醇血症和减少单核细胞趋化来抑制高脂肪饮食引起的动脉粥样硬化
DOI：
10.3389/fphar.2021.719750
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发表时间：
2021
影响因子：
5.6
通讯作者：
Han J
中科院分区：
文献类型：
--
作者：
Chen Y;Su J;Yan Y;Zhao Q;Ma J;Zhu M;He X;Zhang B;Xu H;Yang X;Duan Y;Han J
动脉粥样硬化是心血管疾病(CVD)的主要病理基础。临床上，间歇性禁食(IF)可以降低心血管疾病的风险。然而，IF在动脉粥样硬化发生发展中的作用尚未完全阐明。在此，我们确定了IF对高脂饮食诱导的促动脉粥样硬化低密度脂蛋白受体缺陷(LDLR-/-)小鼠动脉粥样硬化的保护作用及其可能的机制。LDLR-/-小鼠按3d自由喂养和1d禁食的间歇性禁食周期，对照组给予HFD连续灌胃。疗程为7周(∼12周期)或14周(∼24周期)。与减少HFD总摄入量有关，如果大幅减少，内侧主动脉和主动脉根窦的损害。它还通过增加平滑肌细胞(SMC)/胶原含量和纤维帽厚度增加斑块稳定性，同时减少巨噬细胞聚集和坏死核心区域。从机理上讲，IF通过抑制肝脏中的胆固醇合成来降低血清总胆固醇和低密度脂蛋白胆固醇水平。同时，IF可减轻HFD所致的肝脏脂质积聚。有趣的是，IF显著降低了循环中的Ly6 Chigh单核细胞而不是T细胞和血清c-c基序趋化因子配体2的水平。在功能上，IF通过抑制VCAM-1和ICAM-1的表达而减少单核细胞与主动脉内皮细胞的黏附。综上所述，我们的研究表明，IF通过减少单核细胞趋化/黏附和改善高胆固醇血症来减轻LDLR-/-小鼠的动脉粥样硬化，并提示其在动脉粥样硬化治疗中的潜在应用。
Atherosclerosis is a major pathology for cardiovascular diseases (CVDs). Clinically, the intermittent fasting (IF) has been observed to reduce the risk of CVDs. However, the effect of IF on the development of atherosclerosis has not been fully elucidated. Herein, we determined the protection of IF against high-fat diet–induced atherosclerosis in pro-atherogenic low-density lipoprotein receptor deficient (LDLR-/-) mice and the potentially involved mechanisms. The LDLR-/- mice were scheduled intermittent fasting cycles of 3-day HFD feeding ad libitum and 1 day fasting, while the mice in the control group were continuously fed HFD. The treatment was lasted for 7 weeks (∼12 cycles) or 14 weeks (∼24 cycles). Associated with the reduced total HFD intake, IF substantially reduced lesions in the en face aorta and aortic root sinus. It also increased plaque stability by increasing the smooth muscle cell (SMC)/collagen content and fibrotic cap thickness while reducing macrophage accumulation and necrotic core areas. Mechanistically, IF reduced serum total and LDL cholesterol levels by inhibiting cholesterol synthesis in the liver. Meanwhile, HFD-induced hepatic lipid accumulation was attenuated by IF. Interestingly, circulating Ly6Chigh monocytes but not T cells and serum c-c motif chemokine ligand 2 levels were significantly reduced by IF. Functionally, adhesion of monocytes to the aortic endothelium was decreased by IF via inhibiting VCAM-1 and ICAM-1 expression. Taken together, our study indicates that IF reduces atherosclerosis in LDLR-/- mice by reducing monocyte chemoattraction/adhesion and ameliorating hypercholesterolemia and suggests its potential application for atherosclerosis treatment.
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DOI：
10.1016/j.carpath.2012.06.006
发表时间：
2013-01
期刊：
Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology
影响因子：
--
作者：
Gimbrone MA Jr;García-Cardeña G
通讯作者：
García-Cardeña G
影响因子：
4
作者：
Bhoumik, Sukanya;Kumar, Raushan;Rizvi, Syed Ibrahim
通讯作者：
Rizvi, Syed Ibrahim
抑制 ERK1/2 和激活 LXR 可协同减少 ApoE 缺陷小鼠的动脉粥样硬化病变。
DOI：
10.1161/atvbaha.114.305116
发表时间：
2015-04-01
影响因子：
8.7
作者：
Chen, Yuanli;Duan, Yajun;Han, Jihong
通讯作者：
Han, Jihong
影响因子：
3.9
作者：
HOTTA, S;CHAIKOFF, IL
通讯作者：
CHAIKOFF, IL
影响因子：
6.3
作者：
Hoddy, Kristin K.;Gibbons, Catherine;Varady, Krista A.
通讯作者：
Varady, Krista A.