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Diabetic disruption of endothelial function
Tetrahydrobiopterin (BH4) is a suspected mediator of reduced endothelial NO synthase activity, which results in endothelial dysfunction characteristic of diabetes. The underlying regulatory mechanism, however, remains incompletely defined. Keith M. Channon and colleagues from John Radcliffe Hospital in Oxford, United Kingdom describe the generation of a novel transgenic mouse with endothelium-specific overexpression of guanosine triphosphatecyclohydrolase I (GTPCH), the rate-limiting enzyme in BH4 synthesis. The authors found that loss of endothelial BH4 in diabetes results from biopterin oxidation, rather than an alteration in biopterin synthesis. Comparison of healthy and diabetic mice revealed that overexpression of GTPCH increases endothelial BH4 synthesis and preserves NO-mediated endothelial function. The data indicate that endothelial BH4 is an important regulator of dysfunctional eNOS regulation in diabetes and represents a rational therapeutic target in the restoration of NO-mediated endothelial function in this and other vascular disease states.
TITLE: Tetrahydrobiopterin-dependent preservation of nitric oxidemediated endothelial function in diabetes by targeted transgenic GTPcyclohydrolase I overexpression
AUTHOR CONTACT:
Keith Channon
John Radcliffe Hospital, Oxford, United Kingdom
Phone : 44-1865-851085
Fax : 44-1865-222077
E-mail: keith.channon@cardiov.ox.ac.uk
View the PDF of this article at: https://www.the-jci.org/press/17786.pdf
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Will the real phosphatonin please stand up
A novel circulation phosphaturic hormone is postulated to regulate systemic phosphate homeostasis. Two new studies reveal prot
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Contact: Brooke Grindlinger
science_editor@the-jci.org
212-342-9006
Journal of Clinical Investigation
2-Sep-2003