New Target for Treating Diabetic Cardiomyopathy Identified

Advances in understanding diabetic cardiomyopathy have revealed a potential therapeutic target for a disease that currently has no specific treatments.

Diabetic cardiomyopathy, a progressive heart condition that is independent of hypertension or other cardiovascular disorders, is one of the leading causes of death among individuals with diabetes. Despite its prevalence in both type 1 and type 2 diabetes, this underdiagnosed condition lacks specific drug treatments or clinical guidelines. However, a study published in Pharmacological Research has identified the nuclear receptor protein PPARβ/δ as a potential target for developing therapies to combat the condition.

A Key Player in Disease Progression

Diabetic cardiomyopathy is linked to metabolic dysregulation, inflammation, fibrosis, and cardiac cell death caused by hyperglycemia and lipotoxicity. The study demonstrated that activating PPARβ/δ—an abundant receptor in metabolically active tissues such as the heart, liver, and skeletal muscle—can mitigate these harmful processes.

Using animal models and cultured human cardiac cells exposed to hyperglycemic conditions, the researchers showed that activating PPARβ/δ suppresses proinflammatory and profibrotic transcription factors (NF-қB and AP-1) and inhibits the mitogen-activated protein kinase (MAPK) pathway. These pathways are known to accelerate cardiac remodeling, reduce myocardial elasticity, and contribute to contractile dysfunction, which can ultimately lead to heart failure.

The study also suggests that activation of PPARβ/δ could have broader protective effects, not only preventing inflammation and fibrosis in the heart but also potentially safeguarding other organs, such as the liver and kidneys, in related conditions.

Why This Matters

Diabetic cardiomyopathy represents a critical unmet medical need, with limited therapeutic options and high mortality rates. The identification of PPARβ/δ as a protective factor provides a strong foundation for the development of targeted therapies. According to Professor Manuel Vázquez-Carrera, one of the study’s lead authors, activating this receptor may restore metabolic balance and improve cardiac function in patients with diabetes.

The growing interest in PPARβ/δ agonists as a therapeutic class lends further significance to these findings. For instance, the FDA approved seladelpar, a selective PPARβ/δ agonist, in 2024 for treating primary biliary cholangitis, a chronic liver disease. While seladelpar’s success suggests the potential of PPARβ/δ agonists in other diseases, such as diabetic cardiomyopathy, further research and clinical trials will be required to translate these findings into viable treatments.