TY - JOUR
T1 - The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction
T2 - a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe
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
N1 - Funding Information:
M. Shimabukuro designed the study and wrote the manuscript; C.O., S. Yanagi, Y.T. and M. Sato contributed to the measurement for oxycholesterols; H.Y. performed echocardiography; E.U., N.S., H.K., Y.H., J.R.K. and X.L. performed the morphological study; S.T. contributed to CT study; D.F., S. Yagi, T.S., T.K. and H.M. were involved in data interpretation and discussion; M. Sata designed and conducted the study. We are grateful to Ms. Maya Nakagawa for echocardiography; to Ms. Hiromi Sato, Ms. Mayuko Higashida and Dr. Masayoshi Ishida for experimental assistance; and to Ms. Hiroko Gouda, Junko Yata, Yuka Yoneda and Saori Hama for secretarial support. This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology, Japan : Nos. 23591314 , 24591338 , 24591063 and 25293184 , and by a grant from Motor Vehicle Trust Fund for Research of Heart Diseases . M. Sata received financial support from Bayer Yakuhin, Ltd.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/9/1
Y1 - 2016/9/1
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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84978149009&partnerID=8YFLogxK
U2 - 10.1016/j.jnutbio.2016.05.010
DO - 10.1016/j.jnutbio.2016.05.010
M3 - Article
C2 - 27416363
AN - SCOPUS:84978149009
SN - 0955-2863
VL - 35
SP - 66
EP - 73
JO - Nutrition Reports International
JF - Nutrition Reports International
ER -
