Researchers identify novel process involved in development of diabetes-induced heart failure
Researchers at Texas A&M Health Science Center College of Medicine have discovered a novel mechanism in diabetes-induced heart failure, which will provide an alternative target for the treatment and prevention of cardiovascular disease in diabetic patients.
Globally, diabetes affects more than 285 million individuals and by 2030, that number is expected to rise to 439 million. Diabetes increases the risk of heart failure – the leading cause of death in diabetic patients. Most commonly, diabetic patients develop diabetic cardiomyopathy (DCM), a disorder of heart function independent of hypertension or coronary disease. Symptoms of DCM are not present in more than 75 percent of patients with this condition and specific treatment strategies do not exist.
“A heart that does not function well, does not pump well and will eventually lead to heart failure,” said Kenneth M. Baker, M.D., FAHA, FIACS, professor and vice chair at the Texas A&M College of Medicine. “Mechanistically, there is a lack of understanding of this condition, resulting in a lack of treatment options, a devastating reality for millions of patients with diabetes-induced heart disease.”
Retinoic acid is vitamin A’s active breakdown product, and is involved in a wide range of biological processes, such as cell growth, differentiation and cell death. The action of retinoic acid is regulated through binding and activation of two specific nuclear receptors: retinoic acid receptors (RAR) and retinoid X receptors (RXR). Activation of RAR and RXR has been found to suppress the development of obesity, insulin resistance and diabetes. With this knowledge, the team honed in on the role of RAR and RXR in regulation of the development of DCM.
Using a diabetic animal model and cultured heart cells, the team was able to demonstrate that activation of the RAR/RXR pathways lowered the blood glucose level, improved insulin resistance and prevented diabetes-induced heart dysfunction. The team further identified that RAR/RXR pathways were damaged in a diabetic heart, and the impaired RAR/RXR signaling may actually be a trigger to accelerate diabetes-induced development of DCM, by damaging lipid/glucose metabolism and increasing oxidative stress in the heart.
“If we can understand how these abnormal processes occur, we can start targeting certain aspects in the heart to improve function,” Baker said. “This could ultimately lead to therapeutic remedies that either activate or inhibit the pathways that are involved in DCM, allowing us to medically intervene and prevent heart failure from occurring in the first place.”
Next, the team plans to delve further into how these abnormal processes occur by looking at the RAR/RXR pathways and their effects on the heart.
This work, supported by a grant from the National Institutes of Health, has been published in the Journal of Molecular and Cellular Cardiology, the Journal of Cellular Physiology and the American Journal of Physiology, Heart and Circulatory Physiology.