Activation of toll-like receptors and inflammasome complexes in the diabetic cardiomyopathy-associated inflammation

Diabetic cardiomyopathy is defined as a ventricular dysfunction initiated by alterations in cardiac energy substrates in the absence of coronary artery disease and hypertension. Hyperglycemia, hyperlipidemia, and insulin resistance are major inducers of the chronic low-grade inflammatory state that characterizes the diabetic heart. Cardiac Toll-like receptors and inflammasome complexes may be key inducers for inflammation probably through NF- κ B activation and ROS overproduction. However, metabolic dysregulated factors such as peroxisome proliferator-activated receptors and sirtuins may serve as therapeutic targets to control this response by mitigating both Toll-like receptors and inflammasome signalingThis work was supported by National Grants fromMinisterio de Educación y Ciencia (SAF2009-08367), Comunidad de Madrid (CCG10-UAM/BIO-5289), and FISS (PI10/00072

Updating Experimental Models of Diabetic Cardiomyopathy

Diabetic cardiomyopathy entails a serious cardiac dysfunction induced by alterations in structure and contractility of the myocardium. This pathology is initiated by changes in energy substrates and occurs in the absence of atherothrombosis, hypertension, or other cardiomyopathies. Inflammation, hypertrophy, fibrosis, steatosis, and apoptosis in the myocardium have been studied in numerous diabetic experimental models in animals, mostly rodents. Type I and type II diabetes were induced by genetic manipulation, pancreatic toxins, and fat and sweet diets, and animals recapitulate the main features of human diabetes and related cardiomyopathy. In this review we update and discuss the main experimental models of diabetic cardiomyopathy, analysing the associated metabolic, structural, and functional abnormalities, and including current tools for detection of these responses. Also, novel experimental models based on genetic modifications of specific related genes have been discussed. The study of specific pathways or factors responsible for cardiac failures may be useful to design new pharmacological strategies for diabetic patients