Potential Drug Target Identified For Treating Accelerated Atherosclerosis In Diabetes

In T1D, vascular complications such as atherosclerosis, are a major cause of death, so preventing them is a major focus of JDRF’s research program. How diabetes accelerates the process of atherosclerosis is not well known. However, oxidative stress induced by high glucose levels, appears to play a role. The researchers who conducted this study identified an oxidative stress related protein call Nox1 as playing a key and drug-targetable role in the accelerated development of diabetic atherosclerosis. The investigators used human cell cultures and animal models prone to accelerated atherosclerosis in the presence of diabetes and investigated various means to block multiple Nox enzymes. Deleting Nox1 in the mice greatly reduced accelerated atherosclerosis, whereas deleting other related proteins did not. However, blocking the action of Nox1 and Nox4 with a drug-like experimental Nox inhibitor  reduced the development of atherosclerosis in the presence of diabetes. These studies identified a major role for Nox1 in diabetic atherosclerosis and add to prior work demonstrating a role for the Nox family of proteins in diabetic kidney disease.  These results suggest that Nox1-dependent oxidative stress is a promising drug development target for potentially treating or preventing diabetic complications, including atherosclerosis.

Ramifications for Individuals with T1D:

People with T1D are at significantly higher risk for cardiovascular disease than the general population and this complication can also occur at a younger age than in non-diabetics. It is possible that therapies targeting the Nox1 protein, currently in development for diabetic kidney disease, may have additional beneficial effects on cardiovascular disease in individuals with T1D.

JDRF Involvement:

This work was funded in part by JDRF.

Investigators and Institutions:

Karin Jandeleit-Dahm, Rhian Touyz, Mark Cooper and colleagues, Baker IDI Australia, and University of Ottawa

Reference:

Gray SP, Di Marco E, and others. NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis.

Circulation. 2013 May 7;127(18):1888-902. doi: 10.1161/CIRCULATIONAHA.112.132159. Epub 2013 Apr 5.