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

Michio Shimabukuro, Chinami Okawa, Hirotsugu Yamada, Shuhei Yanagi, Etsuko Uematsu, Noriko Sugasawa, Hirotsugu Kurobe, Yoichiro Hirata, Joo ri Kim-Kaneyama, Xiao Feng Lei, Shoichiro Takao, Yasutake Tanaka, Daiju Fukuda, Shusuke Yagi, Takeshi Soeki, Tetsuya Kitagawa, Hiroaki Masuzaki, Masao Sato, Masataka Sata

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)66-73
ページ数8
ジャーナルJournal of Nutritional Biochemistry
35
DOI
出版物ステータス出版済み - 9 1 2016

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Anticholesteremic Agents
Intestinal Absorption
Nutrition
Swine
Fats
Cholesterol
Diet
Liver
Myocardium
Tissue
Cardiomegaly
Tissue Distribution
Ezetimibe
Metabolism
Cardiovascular Diseases
Fatty Acids
Genes
Gene Expression
Food
Enzymes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

これを引用

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. / Shimabukuro, Michio; Okawa, Chinami; Yamada, Hirotsugu; Yanagi, Shuhei; Uematsu, Etsuko; Sugasawa, Noriko; Kurobe, Hirotsugu; Hirata, Yoichiro; Kim-Kaneyama, Joo ri; Lei, Xiao Feng; Takao, Shoichiro; Tanaka, Yasutake; Fukuda, Daiju; Yagi, Shusuke; Soeki, Takeshi; Kitagawa, Tetsuya; Masuzaki, Hiroaki; Sato, Masao; Sata, Masataka.

:: Journal of Nutritional Biochemistry, 巻 35, 01.09.2016, p. 66-73.

研究成果: ジャーナルへの寄稿記事

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 2016, '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', Journal of Nutritional Biochemistry, 巻. 35, pp. 66-73. https://doi.org/10.1016/j.jnutbio.2016.05.010
Shimabukuro, Michio ; Okawa, Chinami ; Yamada, Hirotsugu ; Yanagi, Shuhei ; Uematsu, Etsuko ; Sugasawa, Noriko ; Kurobe, Hirotsugu ; Hirata, Yoichiro ; Kim-Kaneyama, Joo ri ; Lei, Xiao Feng ; Takao, Shoichiro ; Tanaka, Yasutake ; Fukuda, Daiju ; Yagi, Shusuke ; Soeki, Takeshi ; Kitagawa, Tetsuya ; Masuzaki, Hiroaki ; Sato, Masao ; Sata, Masataka. / 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. :: Journal of Nutritional Biochemistry. 2016 ; 巻 35. pp. 66-73.
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abstract = "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.",
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AU - Shimabukuro, Michio

AU - Okawa, Chinami

AU - Yamada, Hirotsugu

AU - Yanagi, Shuhei

AU - Uematsu, Etsuko

AU - Sugasawa, Noriko

AU - Kurobe, Hirotsugu

AU - Hirata, Yoichiro

AU - Kim-Kaneyama, Joo ri

AU - Lei, Xiao Feng

AU - Takao, Shoichiro

AU - Tanaka, Yasutake

AU - Fukuda, Daiju

AU - Yagi, Shusuke

AU - Soeki, Takeshi

AU - Kitagawa, Tetsuya

AU - Masuzaki, Hiroaki

AU - Sato, Masao

AU - Sata, Masataka

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N2 - 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.

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