β-Sitosterol oxidation products attenuate vasorelaxation by increasing reactive oxygen species and cyclooxygenase-2

Chao Yang; Zhen Yu Chen; Siu Ling Wong; Jian Liu; Yin Tong Liang; Chi Wai Lau; Hung Kay Lee; Yu Huang; Suk Ying Tsang

doi:10.1093/cvr/cvs370

β-Sitosterol oxidation products attenuate vasorelaxation by increasing reactive oxygen species and cyclooxygenase-2

Chao Yang
, Zhen Yu Chen
, Siu Ling Wong
, Jian Liu
, Yin Tong Liang
, Chi Wai Lau
, Hung Kay Lee
, Yu Huang
, Suk Ying Tsang

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

43 Citations (Scopus)

Abstract

Aimsβ-Sitosterol has become a popular cholesterol-lowering functional food product worldwide. β-Sitosterol can be oxidized to β-sitosterol oxidation products (SOPs) during food processing. Little is known about the impact of SOPs and β-sitosterol on the functionality of arteries. This study investigated the effects of SOPs and β-sitosterol on vasorelaxation and the possible cellular mechanisms involved.Methods and resultsBy isometric tension measurement, SOPs but not β-sitosterol blunted relaxation induced by acetylcholine or Ca²⁺ ionophore A23187 in endothelium-intact aortae. SOPs-impaired vasorelaxation was completely reversed by cyclooxygenase (COX)-2 inhibitor DuP-697, whereas the reversal by COX-1 inhibitor SC-560 was only partial. Western blotting and immunohistochemistry showed that SOPs increased the protein expression of COX-2 but not COX-1 in the endothelium. Using dihydroethidium staining and electron paramagnetic resonance spin trapping techniques, SOPs were found to elevate the level of reactive oxygen species in rat aortic endothelial cells, and the effects were reversed by antioxidants tempol, tiron, or diphenylene iodonium. Consistently, these antioxidants reversed SOPs-induced impairment of endothelium-dependent relaxation. Up-regulation of COX-2 expression by SOPs was also reversed by tempol. Moreover, SOPs attenuated nitric oxide donor sodium nitroprusside-induced relaxation in endothelium-intact, but not endothelium-denuded rings, confirming that SOPs act on the endothelium. Interestingly, a thromboxane-prostanoid (TP) receptor blocker S18886 reversed SOPs-impaired vasorelaxation, suggesting the involvement of TP receptor in mediating the downstream effect. SOPs decreased cGMP production, and the effect could be reversed by inhibiting COX-2 or TP receptor.ConclusionThis study provides novel experimental evidence showing the harmful effects of SOPs on endothelial function. © 2012 The Author.

Original language	English
Pages (from-to)	520-532
Journal	Cardiovascular Research
Volume	97
Issue number	3
DOIs	https://doi.org/10.1093/cvr/cvs370
Publication status	Published - 1 Mar 2013
Externally published	Yes

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Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

Research Keywords

Beta-sitosterol
Beta-sitosterol oxidation products
Cyclooxygenase-2
Endothelium
Reactive oxygen species

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10.1093/cvr/cvs370

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@article{d9b9bb44a2d849c683dae0e60986c150,

title = "β-Sitosterol oxidation products attenuate vasorelaxation by increasing reactive oxygen species and cyclooxygenase-2",

abstract = "Aimsβ-Sitosterol has become a popular cholesterol-lowering functional food product worldwide. β-Sitosterol can be oxidized to β-sitosterol oxidation products (SOPs) during food processing. Little is known about the impact of SOPs and β-sitosterol on the functionality of arteries. This study investigated the effects of SOPs and β-sitosterol on vasorelaxation and the possible cellular mechanisms involved.Methods and resultsBy isometric tension measurement, SOPs but not β-sitosterol blunted relaxation induced by acetylcholine or Ca2+ ionophore A23187 in endothelium-intact aortae. SOPs-impaired vasorelaxation was completely reversed by cyclooxygenase (COX)-2 inhibitor DuP-697, whereas the reversal by COX-1 inhibitor SC-560 was only partial. Western blotting and immunohistochemistry showed that SOPs increased the protein expression of COX-2 but not COX-1 in the endothelium. Using dihydroethidium staining and electron paramagnetic resonance spin trapping techniques, SOPs were found to elevate the level of reactive oxygen species in rat aortic endothelial cells, and the effects were reversed by antioxidants tempol, tiron, or diphenylene iodonium. Consistently, these antioxidants reversed SOPs-induced impairment of endothelium-dependent relaxation. Up-regulation of COX-2 expression by SOPs was also reversed by tempol. Moreover, SOPs attenuated nitric oxide donor sodium nitroprusside-induced relaxation in endothelium-intact, but not endothelium-denuded rings, confirming that SOPs act on the endothelium. Interestingly, a thromboxane-prostanoid (TP) receptor blocker S18886 reversed SOPs-impaired vasorelaxation, suggesting the involvement of TP receptor in mediating the downstream effect. SOPs decreased cGMP production, and the effect could be reversed by inhibiting COX-2 or TP receptor.ConclusionThis study provides novel experimental evidence showing the harmful effects of SOPs on endothelial function. {\textcopyright} 2012 The Author.",

keywords = "Beta-sitosterol, Beta-sitosterol oxidation products, Cyclooxygenase-2, Endothelium, Reactive oxygen species",

author = "Chao Yang and Chen, \{Zhen Yu\} and Wong, \{Siu Ling\} and Jian Liu and Liang, \{Yin Tong\} and Lau, \{Chi Wai\} and Lee, \{Hung Kay\} and Yu Huang and Tsang, \{Suk Ying\}",

note = "Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].",

year = "2013",

month = mar,

day = "1",

doi = "10.1093/cvr/cvs370",

language = "English",

volume = "97",

pages = "520--532",

journal = "Cardiovascular Research",

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TY - JOUR

T1 - β-Sitosterol oxidation products attenuate vasorelaxation by increasing reactive oxygen species and cyclooxygenase-2

AU - Yang, Chao

AU - Chen, Zhen Yu

AU - Wong, Siu Ling

AU - Liu, Jian

AU - Liang, Yin Tong

AU - Lau, Chi Wai

AU - Lee, Hung Kay

AU - Huang, Yu

AU - Tsang, Suk Ying

N1 - Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Aimsβ-Sitosterol has become a popular cholesterol-lowering functional food product worldwide. β-Sitosterol can be oxidized to β-sitosterol oxidation products (SOPs) during food processing. Little is known about the impact of SOPs and β-sitosterol on the functionality of arteries. This study investigated the effects of SOPs and β-sitosterol on vasorelaxation and the possible cellular mechanisms involved.Methods and resultsBy isometric tension measurement, SOPs but not β-sitosterol blunted relaxation induced by acetylcholine or Ca2+ ionophore A23187 in endothelium-intact aortae. SOPs-impaired vasorelaxation was completely reversed by cyclooxygenase (COX)-2 inhibitor DuP-697, whereas the reversal by COX-1 inhibitor SC-560 was only partial. Western blotting and immunohistochemistry showed that SOPs increased the protein expression of COX-2 but not COX-1 in the endothelium. Using dihydroethidium staining and electron paramagnetic resonance spin trapping techniques, SOPs were found to elevate the level of reactive oxygen species in rat aortic endothelial cells, and the effects were reversed by antioxidants tempol, tiron, or diphenylene iodonium. Consistently, these antioxidants reversed SOPs-induced impairment of endothelium-dependent relaxation. Up-regulation of COX-2 expression by SOPs was also reversed by tempol. Moreover, SOPs attenuated nitric oxide donor sodium nitroprusside-induced relaxation in endothelium-intact, but not endothelium-denuded rings, confirming that SOPs act on the endothelium. Interestingly, a thromboxane-prostanoid (TP) receptor blocker S18886 reversed SOPs-impaired vasorelaxation, suggesting the involvement of TP receptor in mediating the downstream effect. SOPs decreased cGMP production, and the effect could be reversed by inhibiting COX-2 or TP receptor.ConclusionThis study provides novel experimental evidence showing the harmful effects of SOPs on endothelial function. © 2012 The Author.

AB - Aimsβ-Sitosterol has become a popular cholesterol-lowering functional food product worldwide. β-Sitosterol can be oxidized to β-sitosterol oxidation products (SOPs) during food processing. Little is known about the impact of SOPs and β-sitosterol on the functionality of arteries. This study investigated the effects of SOPs and β-sitosterol on vasorelaxation and the possible cellular mechanisms involved.Methods and resultsBy isometric tension measurement, SOPs but not β-sitosterol blunted relaxation induced by acetylcholine or Ca2+ ionophore A23187 in endothelium-intact aortae. SOPs-impaired vasorelaxation was completely reversed by cyclooxygenase (COX)-2 inhibitor DuP-697, whereas the reversal by COX-1 inhibitor SC-560 was only partial. Western blotting and immunohistochemistry showed that SOPs increased the protein expression of COX-2 but not COX-1 in the endothelium. Using dihydroethidium staining and electron paramagnetic resonance spin trapping techniques, SOPs were found to elevate the level of reactive oxygen species in rat aortic endothelial cells, and the effects were reversed by antioxidants tempol, tiron, or diphenylene iodonium. Consistently, these antioxidants reversed SOPs-induced impairment of endothelium-dependent relaxation. Up-regulation of COX-2 expression by SOPs was also reversed by tempol. Moreover, SOPs attenuated nitric oxide donor sodium nitroprusside-induced relaxation in endothelium-intact, but not endothelium-denuded rings, confirming that SOPs act on the endothelium. Interestingly, a thromboxane-prostanoid (TP) receptor blocker S18886 reversed SOPs-impaired vasorelaxation, suggesting the involvement of TP receptor in mediating the downstream effect. SOPs decreased cGMP production, and the effect could be reversed by inhibiting COX-2 or TP receptor.ConclusionThis study provides novel experimental evidence showing the harmful effects of SOPs on endothelial function. © 2012 The Author.

KW - Beta-sitosterol

KW - Beta-sitosterol oxidation products

KW - Cyclooxygenase-2

KW - Endothelium

KW - Reactive oxygen species

UR - https://www.scopus.com/pages/publications/84874253944

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U2 - 10.1093/cvr/cvs370

DO - 10.1093/cvr/cvs370

M3 - RGC 21 - Publication in refereed journal

C2 - 23250922

SN - 0008-6363

VL - 97

SP - 520

EP - 532

JO - Cardiovascular Research

JF - Cardiovascular Research

IS - 3

ER -

β-Sitosterol oxidation products attenuate vasorelaxation by increasing reactive oxygen species and cyclooxygenase-2

Abstract

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