The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe.
The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe.
复制标题
氧化胆固醇在心外膜脂肪堆积和心脏功能障碍中的病理生理学作用：一项对喂食高热量饮食且含有肠道胆固醇吸收抑制剂依折麦布的猪的研究。
DOI：
10.1016/j.jnutbio.2016.05.010
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Sata M.
中科院分区：
文献类型：
--
作者：
Shimabukuro M;Okawa C;Yamada H;Yanagi S;Uematsu E;Sugasawa N;Kurobe H;Hirata Y;Kim-Kaneyama JR;Lei XF;Takao S;Tanaka Y;Fukuda D;Yagi S;Soeki T;Kitagawa T;Masuzaki H;Sato M;Sata M.
食物中的氧化胆固醇（oxocholesterols）被认为是强致动脉粥样硬化成分，但其组织分布和在心血管疾病中的作用尚不清楚。为了研究氧化胆固醇的积累是否与心脏形态和功能相关，以及氧化胆固醇的减少是否可以改善心脏性能，将家养雄性猪随机分配至对照饮食（C）、高热量饮食（HCD）或HCD +依折麦布（肠胆固醇吸收抑制剂）组（HCD + E），并评价：（1）血清和组织中氧胆固醇组分的分布，（2）氧胆固醇相关酶的水平，（3）心旁和心外膜冠状动脉脂肪厚度，和（4）心脏性能。依折麦布治疗8周几乎完全减弱了HCD组肝脏中氧胆固醇的升高，但仅降低了左心室（LV）心肌中4β-羟基胆固醇的水平。依折麦布治疗改变了胆固醇和脂肪酸代谢基因的表达，并显著降低了肝脏中将胆固醇分解代谢为4β-羟基胆固醇的CYP 3A 46的表达。依折麦布治疗改善了HCD组的心外膜脂肪厚度增加和心脏功能受损，且改善与LV心肌中4β-羟基胆固醇水平降低密切相关。总之，HCD组中氧胆固醇的增加与心脏肥大和功能障碍以及心外膜脂肪厚度的增加密切相关。依折麦布可直接降低肝脏和左室心肌中的氧化胆固醇，改善心脏形态和功能。
Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD + Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD + E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8 weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4β-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4β-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 4β-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function.