Ryanodine receptor and immune‐related molecules in diabetic cardiomyopathy

Hyperglycaemia is a major aetiological factor in the development of diabetic cardiomyopathy. Excessive hyperglycaemia increases the levels of reactive carbonyl species (RCS), reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the heart and causes derangements in calcium homeostasis, inflammation and immune‐system disorders. Ryanodine receptor 2 (RyR2) plays a key role in excitation–contraction coupling during heart contractions, including rhythmic contraction and relaxation of the heart. Cardiac inflammation has been indicated in part though interleukin 1 (IL‐1) signals, supporting a role for B and T lymphocytes in diabetic cardiomyopathy. Some of the post‐translational modifications of the ryanodine receptor (RyR) by RCS, ROS and RNS stress are known to affect its gating and Ca(2+) sensitivity, which contributes to RyR dysregulation in diabetic cardiomyopathy. RyRs and immune‐related molecules are important signalling species in many physiological and pathophysiological processes in various heart and cardiovascular diseases. However, little is known regarding the mechanistic relationship between RyRs and immune‐related molecules in diabetes, as well as the mechanisms mediating complex communication among cardiomyocytes, fibroblasts and immune cells. This review highlights new findings on the complex cellular communications in the pathogenesis and progression of diabetic cardiomyopathy. We discuss potential therapeutic applications targeting RyRs and immune‐related molecules in diabetic complications.