Review of research progress and drug intervention of endoplasmic reticulum stress in diabetic cardiomyopathy

Diabetic cardiomyopathy(DCM)is defined as the presence of left ventricular dysfunction beyond that which can be accounted for by arterial hypertension,coronary artery disease or evidence of any other structural cardiac disease in individuals with diabetes.DCM is a common consequence of longstanding type 2 diabetes mellitus and encompasses structural,morphological,functional and metabolic abnormalities in the heart.Endoplasmic reticulum(ER) is an organelle entrusted with lipid synthesis,calcium homeostasis,protein folding,and maturation.Perturbation of ER-associated functions results in an evolutionarily conserved cell stress responses,which is called ER stress.ER stress is aimed initially at compensating for damage through three transmembrane proteins including IRE-1,ATF6,PERK and their downstream pro-survival signals,but can eventually trigger cell death if ER stress is excessive or prolonged via apoptotic pathways mediated by CHOP,Caspase-12 and JNK.The mechanisms of the development of diabetic cardiomyopathy are still highly elusive.Now it is known that apoptosis induced by ER stress has been considered to play a role in DCM.Moreover,hyperglycemia,FFAs and inflammation may be the triggers of ER stress.In order to explore the specific therapies for DCM,in recent years scientists from different countries have found that many drugs could alleviate cardiomyocyte apoptosis and improve the function of heart by inhibiting ER stress.Therefore,this paper will summarize the information focused on mechanisms of ER stress in the development of diabetic cardiomyopathy and several drug interventions which can reduce the ER stress by different ways.