A REENT study has highlighted a promising therapeutic target for diabetic cardiomyopathy, a serious yet often under-diagnosed condition affecting heart function in patients with Type 1 and Type 2 diabetes.
Led by researchers from the University of Barcelona (UB), Spain, the study focuses on the nuclear receptor PPARβ/δ, a protein abundant in metabolically active tissues such as the heart. Activation of this protein shows potential in slowing inflammation, fibrosis, and cardiac remodelling, key contributors to diabetic cardiomyopathy.
Unlike other heart conditions, diabetic cardiomyopathy develops independently of hypertension or traditional cardiovascular diseases. It is driven by metabolic imbalances, inflammation, and lipotoxicity caused by hyperglycaemia. This results in cardiac stiffness, impaired relaxation, and ultimately heart failure.
Professor Vázquez-Carrera explained that diabetic myocardium predominantly relies on fatty acid oxidation for energy, leading to lipid accumulation and toxic effects in heart tissue. These stressors activate pro-inflammatory and pro-fibrotic pathways, such as NF-қB and AP-1, further exacerbating heart damage.
The study reveals that PPARβ/δ activation can counteract these effects by inhibiting MAPK pathways, reducing inflammation and fibrosis. These findings were confirmed through experiments on human cardiac cells under hyperglycaemic conditions.
The researchers note parallels with the selective PPARβ/δ agonist seladelpar, which the US Food and Drug Administration approved in August 2024 for treating primary biliary cholangitis. While its application in Europe is under review, the success of seladelpar demonstrates the pharmaceutical potential of targeting PPARβ/δ in chronic diseases.
With no current specific treatment for diabetic cardiomyopathy, these findings could inspire the development of targeted drugs, offering new hope for patients. “Pharmaceutical companies may now see the value in advancing research on PPARβ/δ agonists to address this life-threatening condition,” the researchers concluded.
This breakthrough offers a promising avenue for tackling one of the leading causes of death in diabetic patients, underscoring the urgent need for further clinical investigation.
Victoria Antoniou, EMJ
Reference
Rostami A et al. PPARβ/δ prevents inflammation and fibrosis during diabetic cardiomyopathy. V Pharmacol Res. 2024:210:107515.
