Idioma:

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

Watson, A. M. D. ; Olukman, M. ; Koulis, C. ; Tu, Y. ; Samijono, D. ; Yuen, D. ; Lee, C. ; Behm, D. J. ; Cooper, M. E. ; Jandeleit-Dahm, K. A. M. ; Calkin, A. C. ; Allen, T. J.

Diabetologia, 2013-05, Vol.56 (5), p.1155-1165 [Periódico revisado por pares]

Berlin/Heidelberg: Springer-Verlag

Texto completo disponível

Citações Citado por

Enviar para

Título:
Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes
Autor: Watson, A. M. D. ; Olukman, M. ; Koulis, C. ; Tu, Y. ; Samijono, D. ; Yuen, D. ; Lee, C. ; Behm, D. J. ; Cooper, M. E. ; Jandeleit-Dahm, K. A. M. ; Calkin, A. C. ; Allen, T. J.
Assuntos: Animals ; Aorta - drug effects ; Aorta - immunology ; Aorta - metabolism ; Aorta - pathology ; Atherosclerosis ; Atherosclerosis (general aspects, experimental research) ; Atherosclerosis - complications ; Atherosclerosis - metabolism ; Atherosclerosis - pathology ; Atherosclerosis - prevention & control ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cell Adhesion - drug effects ; Cells, Cultured ; Crosses, Genetic ; Diabetes ; Diabetes Mellitus, Type 1 - complications ; Diabetes. Impaired glucose tolerance ; Diabetic Angiopathies - immunology ; Diabetic Angiopathies - metabolism ; Diabetic Angiopathies - pathology ; Diabetic Angiopathies - prevention & control ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - immunology ; Endothelium, Vascular - metabolism ; Endothelium, Vascular - pathology ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Glucose ; Human Physiology ; Human Umbilical Vein Endothelial Cells - drug effects ; Human Umbilical Vein Endothelial Cells - immunology ; Human Umbilical Vein Endothelial Cells - metabolism ; Human Umbilical Vein Endothelial Cells - pathology ; Humans ; Internal Medicine ; Male ; Medical research ; Medical sciences ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes - drug effects ; Monocytes - immunology ; Peptides ; Pilot Projects ; Preventive medicine ; Protective Agents - pharmacology ; Protective Agents - therapeutic use ; Proteins ; Receptors, G-Protein-Coupled - antagonists & inhibitors ; Receptors, G-Protein-Coupled - metabolism ; Sulfonamides - pharmacology ; Sulfonamides - therapeutic use ; Urotensins - antagonists & inhibitors ; Urotensins - biosynthesis ; Urotensins - metabolism
É parte de: Diabetologia, 2013-05, Vol.56 (5), p.1155-1165
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: 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 high-glucose (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 mg kg −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.
Editor: Berlin/Heidelberg: Springer-Verlag
Idioma: Inglês

Links

Voltar para lista de resultados

Anterior Resultado 9 Avançar Ir para próxima página

Realização: Logos de Redes Sociais:

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

Watson, A. M. D. ; Olukman, M. ; Koulis, C. ; Tu, Y. ; Samijono, D. ; Yuen, D. ; Lee, C. ; Behm, D. J. ; Cooper, M. E. ; Jandeleit-Dahm, K. A. M. ; Calkin, A. C. ; Allen, T. J.

Berlin/Heidelberg: Springer-Verlag

Buscando em bases de dados remotas. Favor aguardar.