The prevalence of obesity and diabetes is increasing worldwide and diabetes currently represents the leading cause of blindness, renal failure, and amputation in the USA. However, these conditions can be slowed or prevented by controlling glucose levels within the body. Interestingly, individuals with diabetes have a two to four-fold higher risk of developing heart disease. However, to date, scientists have been unable to determine how high levels of glucose lead to excess cardiovascular risk. Surprisingly, the treatment of hyperglycemia, exclusive of other heart disease intervention protocols, is currently inadequate to reverse or reduce heart disease. In the October 1 issue of the Journal of Clinical Investigation, a study by Michael A. Brownlee and colleagues from Albert Einstein College of Medicine in New York, reveals a new target – an enzyme called PARP – that is dysregulated by high glucose levels, resulting in increased oxidative stress, which effects endothelial cells lining the heart and blood vessels. The authors demonstrated that inhibition of PARP activation blocked all the known pathways of hyperglycemia-induced vascular damage, suggesting that PARP inhibitors might have unique clinical efficacy in preventing the development and progression of diabetic complications of the cardiovascular system.
In an accompanying commentary, Jane Reusch from the University of Colorado Health Sciences Center comments "with the incidence of diabetes and its complications on the rise, these results offer hope for new treatments in the foreseeable future".
###
TITLE: Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells
AUTHOR CONTACT:
Michael A. Brownlee
Albert Einstein College of Medicine, New York, New York, USA.
Phone: 718-430-3636
Fax: 718-430-8570
Email: brownlee@aecom.yu.edu
View the PDF of this article at: http://www.jci.org/cgi/content/full/112/7/1049
ACCOMPANYING COMMENTARY:
Diabetes, microvascular complications, and cardiovascular complications: what is it about glucose?
AUTHOR CONTACT:
Jane E. B. Reusch
Veterans Affairs Medical Center, Denver, Colorado, USA.
Phone: 303-399-8020 ext. 2775
Fax: 303-393-5271
Email: jane.reusch@uchsc.edu
Journal
Journal of Clinical Investigation
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.
