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学科主题基础医学
Unconjugated Bilirubin Mediates Heme Oxygenase-1-Induced Vascular Benefits in Diabetic Mice
Liu, Jian1,2; Wang, Li1,2; Tian, Xiao Yu1,2; Liu, Limei3; Wong, Wing Tak4; Zhang, Yang1,2; Han, Quan-Bin5; Ho, Hing-Man5; Wang, Nanping6; Wong, Siu Ling1,2; Chen, Zhen-Yu7; Yu, Jun8; Ng, Chi-Fai9; Yao, Xiaoqiang1,2; Huang, Yu1,2
刊名DIABETES
2015-05-01
DOI10.2337/db14-1391
64期:5页:1564-1575
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
资助者Hong Kong Research Grants Council ; National Basic Research Program of China ; Natural Science Foundation of China ; Hong Kong Research Grants Council ; National Basic Research Program of China ; Natural Science Foundation of China
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]ENDOTHELIAL PROGENITOR CELLS ; IMPROVES INSULIN SENSITIVITY ; CORONARY-HEART-DISEASE ; METABOLIC SYNDROME ; CARBON-MONOXIDE ; DYSFUNCTION ; SERUM ; HYPERTENSION ; ANTIOXIDANT ; ACTIVATION
英文摘要

Heme oxygenase-1 (HO-1) exerts vasoprotective effects. Such benefit in diabetic vasculopathy, however, remains unclear. We hypothesize that bilirubin mediates HO-1-induced vascular benefits in diabetes. Diabetic db/db mice were treated with hemin (HO-1 inducer) for 2 weeks, and aortas were isolated for functional and molecular assays. Nitric oxide (NO) production was measured in cultured endothelial cells. Hemin treatment augmented endothelium-dependent relaxations (EDRs) and elevated Akt and endothelial NO synthase (eNOS) phosphorylation in db/db mouse aortas, which were reversed by the HO-1 inhibitor SnMP or HO-1 silencing virus. Hemin treatment increased serum bilirubin, and ex vivo bilirubin treatment improved relaxations in diabetic mouse aortas, which was reversed by the Akt inhibitor. Biliverdin reductase silencing virus attenuated the effect of hemin. Chronic bilirubin treatment improved EDRs in db/db mouse aortas. Hemin and bilirubin reversed high glucose-induced reductions in Akt and eNOS phosphorylation and NO production. The effect of hemin but not bilirubin was inhibited by biliverdin reductase silencing virus. Furthermore, bilirubin augmented EDRs in renal arteries from diabetic patients. In summary, HO-1-induced restoration of endothelial function in diabetic mice is most likely mediated by bilirubin, which preserves NO bioavailability through the Akt/eNOS/NO cascade, suggesting bilirubin as a potential therapeutic target for clinical intervention of diabetic vasculopathy.

语种英语
所属项目编号CUHK2/CRF/128 ; T12-402/13-N ; T12-705/11 ; 2012CB517805 ; 91339117
资助者Hong Kong Research Grants Council ; National Basic Research Program of China ; Natural Science Foundation of China ; Hong Kong Research Grants Council ; National Basic Research Program of China ; Natural Science Foundation of China
WOS记录号WOS:000353431200013
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60785
专题基础医学院_心血管所
作者单位1.Chinese Univ Hong Kong, Shenzhen Res Inst, Inst Vasc Med, Hong Kong, Hong Kong, Peoples R China
2.Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100871, Peoples R China
4.Houston Methodist Res Inst, Dept Cardiovasc Sci, Houston, TX USA
5.Hong Kong Baptist Univ, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China
6.Peking Univ, Inst Cardiovasc Sci, Beijing 100871, Peoples R China
7.Chinese Univ Hong Kong, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China
8.Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China
9.Chinese Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China
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GB/T 7714
Liu, Jian,Wang, Li,Tian, Xiao Yu,et al. Unconjugated Bilirubin Mediates Heme Oxygenase-1-Induced Vascular Benefits in Diabetic Mice[J]. DIABETES,2015,64(5):1564-1575.
APA Liu, Jian.,Wang, Li.,Tian, Xiao Yu.,Liu, Limei.,Wong, Wing Tak.,...&Huang, Yu.(2015).Unconjugated Bilirubin Mediates Heme Oxygenase-1-Induced Vascular Benefits in Diabetic Mice.DIABETES,64(5),1564-1575.
MLA Liu, Jian,et al."Unconjugated Bilirubin Mediates Heme Oxygenase-1-Induced Vascular Benefits in Diabetic Mice".DIABETES 64.5(2015):1564-1575.
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