Chronic urotensin II infusion enhances macrophage foam cell formation and atherosclerosis in apolipoprotein E-knockout mice

Shiraishi, Yuji; Watanabe, Takuya; Suguro, Toshiaki; Nagashima, Masaharu; Kato, Ryuichi; Hongo, Shigeki; Itabe, Hiroyuki; Miyazaki, Akira; Hirano, Tsutomu; Adachi, Mitsuru

doi:10.1097/hjh.0b013e32830b61d8

Cited by 31 publications

(40 citation statements)

References 51 publications

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“…Apoe / mice at 9 weeks of age were purchased from Sankyo Laboratory (Tokyo, Japan). The mice were maintained on an atherogenic diet containing 30% fat, 20% sucrose, 0.15% cholesterol, and 8% NaCl (Oriental Yeast, Tokyo, Japan) 13) throughout the experimental period to exacerbate atherosclerosis. After 4 weeks, the mice were randomly assigned to 5 treatment groups: saline (control), Ang , Ang GLP-1, Ang GIP, and Ang DPP-4I (MK0626; gifted by Merck Sharp & Dohme Corp., NJ, USA).…”

Section: Animal Modelmentioning

confidence: 99%

A Dipeptidyl Peptidase-4 Inhibitor but not Incretins Suppresses Abdominal Aortic Aneurysms in Angiotensin II-Infused Apolipoprotein E-Null Mice

Kohashi

Hiromura

Mori

et al. 2016

JAT

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Section: Animal Modelmentioning

confidence: 99%

A Dipeptidyl Peptidase-4 Inhibitor but not Incretins Suppresses Abdominal Aortic Aneurysms in Angiotensin II-Infused Apolipoprotein E-Null Mice

Kohashi

Hiromura

Mori

et al. 2016

JAT

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“…Additionally, chronic UII infusion has been shown to enhance macrophage foam cell formation [12] and atherosclerosis in high-fat-fed Apoe knockout (KO) mice [13]. While UT antagonism has been investigated in diabetic nephropathy [14,15], little is known of the role of UII in the development of diabetes-associated atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes

et al. 2013

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Aims/hypothesis The small, highly conserved vasoactive peptide urotensin II (UII) is upregulated in atherosclerosis. However, its effects in diabetes-associated atherosclerosis have not been assessed. Methods Endothelial cells were grown in normal-and highglucose (5 and 25 mmol/l) media with and without UII (10 −8 mol/l) and/or the UII receptor antagonist, SB-657510 (10 −8 mol/l). Apoe knockout (KO) mice with or without streptozotocin-induced diabetes were treated with or without SB-657510 (30 mgkg −1 day −1 ; n=20 per group) and followed for 20 weeks. Carotid endarterectomy specimens from diabetic and non-diabetic humans were also evaluated. Results In high (but not normal) glucose medium, UII significantly increased CCL2 (encodes macrophage chemoattractant protein 1 [MCP-1]) gene expression (human aortic endothelial cells) and increased monocyte adhesion (HUVECs). UII receptor antagonism in diabetic Apoe KO mice significantly attenuated diabetes-associated atherosclerosis and aortic staining for MCP-1, F4/80 (macrophage marker), cyclooxygenase-2, nitrotyrosine and UII. UII staining was significantly increased in carotid endarterectomies from diabetic compared with non-diabetic individuals, as was staining for MCP-1. Conclusions/interpretation This is the first report to demonstrate that UII is increased in diabetes-associated atherosclerosis in humans and rodents. Diabetes-associated plaque development was attenuated by UII receptor antagonism in the experimental setting. Thus UII may represent a novel therapeutic target in the treatment of diabetes-associated atherosclerosis.

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“…U accelerates macrophage foam cell formation by up-regulating acyl-CoA:cholesterol acyltransferase-1 38) , and has synergistic interactions with mildly oxidized LDL in inducing VSMC proliferation at the highest rate among vasoactive agents 40) . Our recent study showed that chronic infusion of U into apoE-knockout mice enhances atherosclerotic lesions 41) . These findings indicate that U contributes to the progression of atherosclerosis in the large and small cerebral arteries, leading to the major etiology of CVD followed by VaD.…”

Section: Vsmc Mø Mømentioning

confidence: 99%

Increased Plasma Urotensin-II and Carotid Atherosclerosis are Associated with Vascular Dementia

Ban

Watanabe

Suguro

et al. 2009

JAT

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Aim: Human urotensin-(U ) is a cyclic neuropeptide with potent vasoconstrictive activity in the vasculature. The expression of U and its receptor (UT) mRNA is detected at high levels in the brain. We evaluated the relationship between plasma U levels and vascular dementia (VaD) caused by stroke or atherosclerotic small vessel disease. Methods: Carotid artery intima-media thickness (IMT), plaques, plasma levels of immunoreactive U (IR-U ), and atherosclerotic biomarkers were determined in 42 patients with VaD, 197 with Alzheimer's disease (AD), and 47 non-demented elderly controls. Results: Age, gender, body mass index, systolic blood pressure (SBP), fasting plasma glucose, insulin, triglycerides, high-density lipoprotein cholesterol, leptin, and plasminogen activator inhibitor-1 levels were not significantly different among these groups. IR-U , low-density lipoprotein (LDL) cholesterol, lipoprotein(a), lipid peroxides, interleukin-6, and high-sensitive C-reactive protein (hs-CRP) levels, and maximum IMT were significantly higher in VaD than in AD patients or controls. IR-U level showed a significantly positive correlation with SBP or maximum IMT. Multivariate logistic regression analysis revealed a significantly independent association between IR-U levels or increased maximum IMT ( ≥ 1.1 mm) and VaD as compared with SBP, LDL cholesterol, and interleukin-6 levels. Conclusion: Increased plasma IR-U levels and carotid atherosclerosis may be involved in the pathogenesis and progression of VaD.

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Chronic urotensin II infusion enhances macrophage foam cell formation and atherosclerosis in apolipoprotein E-knockout mice

Cited by 31 publications

References 51 publications

A Dipeptidyl Peptidase-4 Inhibitor but not Incretins Suppresses Abdominal Aortic Aneurysms in Angiotensin II-Infused Apolipoprotein E-Null Mice

A Dipeptidyl Peptidase-4 Inhibitor but not Incretins Suppresses Abdominal Aortic Aneurysms in Angiotensin II-Infused Apolipoprotein E-Null Mice

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes

Increased Plasma Urotensin-II and Carotid Atherosclerosis are Associated with Vascular Dementia

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