Utilization of lipoxins and other specialised pro-resolving mediators in the prevention and treatment of diabetic nephropathy and diabetic cardiovascular disease

Abstract

Diabetes mellitus type 2 is a chronic disease caused by insulin resistance. Whilst first originating in the adipose tissue, this pathophysiological process later affects the muscles and the liver as well. This induces high plasma levels of glucose and fatty acids, leading to the inflammatory-related chronic complications of diabetes, such as diabetic nephropathy and diabetic cardiovascular disease. Specialized pro-resolving mediators are lipid mediators responsible for resolving inflammation and could therefore be beneficial in the management of chronic diabetes complications. The aim of this review is to assess if specialised pro-resolving mediators have the potential to attenuate the chronic complications of diabetes. Specialised pro-resolving mediators, especially lipoxins, can modulate both diabetic nephropathy and diabetic cardiovascular disease. In mice it was demonstrated that, at the glomerular level, lipoxins reduced collagen deposition and expression of pro-inflammatory markers. In human saphenous vein smooth muscle cells instead, lipoxins were able to reduce collagen deposition and vascular smooth muscle cells proliferation and chemotaxis. Aspirin is a medication that could be used to modulate specialised pro-resolving mediator levels, as aspirin triggered-specialised pro-resolving mediators exist. Aspirin triggered-specialised pro-resolving mediators are pro-resolving substances with similar effects, but synthetised in a different way, requiring the partial blockage of the cyclooxygenase 2 enzyme. These results demonstrate how such substances could be useful in the treatment of diabetic patients and why further research is needed to create efficient and economical medications.

Keywords: “diabetes mellitus type 2”, “chronic complications of diabetes mellitus”, “specialised pro-resolving mediators”, “inflammation resolution”, “obesity-associated inflammation”