Therapeutic approaches to diabetic cardiomyopathy: Targeting the antioxidant pathway

•PGC-1α increases production of the HO-1 which has a major role in protecting the heart against oxidative stress, microcirculation and mitochondrial dysfunction.•EETs analogues may be helpful to protect the diabetic heart through the activation of Peroxisome Proliferator-Activated Receptor gamma Coactivator-1α (PGC-1α) and Heme Oxygenase (HO-1).•The activation of the EETs PGC-1α -HO-1 axis improves mitochondrial function which is impaired in the diabetic heart, alleviates the oxidative stress and inhibits apoptosis.•HO-1 upregulates EET and PGC1α to increase mitochondrial biogenesis and integrity, which inhibits Fatty acids synthesis and the accumulation of large adipocytes, thus preventing or reducing progression diabetic related factors resulting catdiomyopathy.•HO-1 has been shown is involved in ameliorating insulin resistance, inflammation, fibrosis, cardiac hypertrophy and increases metabolic function. The global epidemic of cardiovascular disease continues unabated and remains the leading cause of death both in the US and worldwide. We hereby summarize the available therapies for diabetes and cardiovascular disease in diabetics. Clearly, the current approaches to diabetic heart disease often target the manifestations and certain mediators but not the specific pathways leading to myocardial injury, remodeling and dysfunction. Better understanding of the molecular events determining the evolution of diabetic cardiomyopathy will provide insight into the development of specific and targeted therapies. Recent studies largely increased our understanding of the role of enhanced inflammatory response, ROS production, as well as the contribution of Cyp-P450-epoxygenase-derived epoxyeicosatrienoic acid (EET), Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α (PGC-1α), Heme Oxygenase (HO)-1 and 20-HETE in pathophysiology and therapy of cardiovascular disease. PGC-1α increases production of the HO-1 which has a major role in protecting the heart against oxidative stress, microcirculation and mitochondrial dysfunction. This review describes the potential drugs and their downstream targets, PGC-1α and HO-1, as major loci for developing therapeutic approaches beside diet and lifestyle modification for the treatment and prevention of heart disease associated with obesity and diabetes.