Reversing diabetic atherosclerosis
Diabetes worsens atherosclerosis and this effect fails to improve even when the blood glucose level returns to normal. A new study shows that macrophages in atherosclerotic plaques ‘remember’ high glucose and suggests a way to overcome this memory.
Diabetes increases the risk of cardiovascular diseases among many other complications. Diabetic patients often develop atherosclerosis that is characterized by excessive deposition of fatty plaques on the inner artery walls. Intriguingly, unlike in non-diabetic patients, reducing blood levels of harmful lipids do not shrink plaques in diabetic patients.
One can speculate that abundant blood glucose may be responsible for the progression of diabetic atherosclerosis. However, diabetic atherosclerosis fails to improve even when the blood glucose level returns to normal (hyperglycaemic memory). These observations suggest that mechanisms independent of both blood lipids and glucose may contribute to diabetic atherosclerosis.
In their latest publication in Communications Biology, Khurrum Shahzad et al. aimed to find a potential intervention that ameliorates the progression of diabetic atherosclerosis. Given protective effects of activated protein C in diabetic kidney disease, they hypothesized that impaired generation of activated protein C in diabetes mellitus may be responsible for the hyperglycaemic memory.
Considering that p66Shc, a redox regulator, has been linked with diabetes-associated vascular complications, this new study shows that p66Shc in plaque macrophages drives the hyperglycaemic memory, which can be reversed by activated protein C. This study demonstrates that reversal of the hyperglycaemic memory in diabetic atherosclerosis is feasible and suggests a potential therapeutic target.
By: Jung-Eun Lee/Communications Biology