Protein Block Stops Vascular Damage in Diabetes

The study was initiated following previous studies that showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin.

The study showed that NFAT activation resulted in 2.2 fold increase in aortic atherosclerosis and enhanced proinflammatory burden. Subsequent in vivo treatment with the NFAT blocker A-285222 for four weeks completely inhibited the diabetes-induced aggravation of atherosclerosis, while having no effect in nondiabetic mice. The STZ-treated mice also exhibited hyperglycemia and higher plasma cholesterol and triglycerides, but these were unaffected by A-285222. In fact, the substance did not affect NFAT in any other cells or organs, ruling out systemic immunosuppression as the mechanism behind reduced atherosclerosis. The study was published in the June 3, 2013, issue of PLOS one.

“That is important. We don’t want to suppress the whole immune system. We also saw that the substance only has an effect when NFAT is active. The plaque formation was only stopped in diabetic mice and not in nondiabetic mice, which had normal blood sugar levels”, said lead author Anna Zetterqvist, MSc. “It appears that there are different mechanisms behind plaque formation caused by diabetes and not caused by diabetes.”

A wealth of epidemiologic evidence demonstrate that hyperglycemia promotes a widespread and aggressive form of atherosclerosis in the coronary arteries, lower extremities, and extracranial carotid arteries of diabetic patients, causing nearly 80% of all deaths and much of their disability. Both diabetes type 1 and type 2 are independent risk factors for myocardial infarction (MI), peripheral vascular disease (PVD), and stroke. In addition, recent studies also show a causal association between elevated glucose levels and increased carotid intima-media thickness, a marker of subclinical atherosclerosis.

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