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; Liu, Xiao; Sugiyama, Takao; Tanaka, Yasutake; Fukuda, Daiju; Yagi, Shusuke; Soeki, Takeshi; Kitagawa, Tetsuya; Masuzaki, Hiroaki; Sato, Masao; Sata, Masataka

doi:10.1016/j.jnutbio.2016.05.010

Cited by 16 publications

(11 citation statements)

References 32 publications

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“…The domestic pig and mini-pig are conventional models of study in pharmacology, imaging and cardiovascular surgery [74,268]. The pig is often a source of vascular wall and ocular cells that have made it possible to characterize the effects of different oxysterols, such as 7KC and 7β-OHC.…”

Section: Pigmentioning

confidence: 99%

7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity

Véjux

Abed-Vieillard

Hajji

et al. 2020

Biochemical Pharmacology

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Section: Pigmentioning

confidence: 99%

7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity

Véjux

Abed-Vieillard

Hajji

et al. 2020

Biochemical Pharmacology

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“…Third, the ROC results cannot be applied broadly to patients with suspected CAD, and the sensitivity and specificity of EATLAD for diagnosing CAD need to be confirmed in a future, larger study. Fourth, we did not consider the impact of medication [33][34][35] or lifestyle 36 on EAT.…”

Section: Study Limitationsmentioning

confidence: 99%

Local Thickness of Epicardial Adipose Tissue Surrounding the Left Anterior Descending Artery Is a Simple Predictor of Coronary Artery Disease　― New Prediction Model in Combination With Framingham Risk Score ―

Maimaituxun

Shimabukuro

Fukuda

et al. 2018

Circ J

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“…informing the extrahepatic tissues about the cholesterol concentration in liver. This notion is supported by the finding in swine that a high-cholesterol diet resulting in doubling of the hepatic cholesterol concentration increased 4bHC 18-fold in serum and 21-fold in cardiac left ventricle (Shimabukuro et al, 2016). LXR agonists are known to activate reverse cholesterol transport (RCT), a beneficial pathway transporting cholesterol from periphery to the liver and intestine for excretion (Temel and Brown, 2015).…”

Section: Discussionmentioning

confidence: 91%

4β-Hydroxycholesterol Signals From the Liver to Regulate Peripheral Cholesterol Transporters

et al. 2020

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Activation of pregnane X receptor (PXR) elevates circulating 4b-hydroxycholesterol (4bHC), an agonist of liver X receptor (LXR). PXR may also regulate 25-hydroxycholesterol and 27hydroxycholesterol. Our aim was to elucidate the roles of PXR and oxysterols in the regulation of cholesterol transporters. We measured oxysterols in serum of volunteers dosed with PXR agonist rifampicin 600 mg/day versus placebo for a week and analyzed the expression of cholesterol transporters in mononuclear cells. The effect of 4bHC on the transport of cholesterol and the expression of cholesterol transporters was studied in human primary monocyte-derived macrophages and foam cells in vitro. The expression of cholesterol transporters was measured also in rat tissues after dosing with a PXR agonist. The levels of 4bHC were elevated, while 25-hydroxycholesterol and 27-hydroxycholesterol remained unchanged in volunteers dosed with rifampicin. The expression of ATP binding cassette transporter A1 (ABCA1) was induced in human mononuclear cells in vivo. The influx of cholesterol was repressed by 4bHC, as was the expression of influx transporter lectin-like oxidized LDL receptor-1 in vitro. The cholesterol efflux and the expression of efflux transporters ABCA1 and ABCG1 were induced. The expression of inducible degrader of the LDL receptor was induced. In rats, PXR agonist increased circulating 4bHC and expression of LXR targets in peripheral tissues, especially ABCA1 and ABCG1 in heart. In conclusion, PXR activation-elevated 4bHC is a signaling molecule that represses cholesterol influx and induces efflux. The PXR-4bHC-LXR pathway could link the hepatic xenobiotic exposure and the regulation of cholesterol transport in peripheral tissues.

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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

Cited by 16 publications

References 32 publications

7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity

7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity

Local Thickness of Epicardial Adipose Tissue Surrounding the Left Anterior Descending Artery Is a Simple Predictor of Coronary Artery Disease　― New Prediction Model in Combination With Framingham Risk Score ―

4β-Hydroxycholesterol Signals From the Liver to Regulate Peripheral Cholesterol Transporters

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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

Cited by 16 publications

References 32 publications

7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity

7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity

Local Thickness of Epicardial Adipose Tissue Surrounding the Left Anterior Descending Artery Is a Simple Predictor of Coronary Artery Disease ― New Prediction Model in Combination With Framingham Risk Score ―

4β-Hydroxycholesterol Signals From the Liver to Regulate Peripheral Cholesterol Transporters

Contact Info

Product

Resources

About

Local Thickness of Epicardial Adipose Tissue Surrounding the Left Anterior Descending Artery Is a Simple Predictor of Coronary Artery Disease　― New Prediction Model in Combination With Framingham Risk Score ―