A collaborative study by the Centre for Biomedical Research Network (CIBER) at the Sant Pau Research Institute (IR Sant Pau) and the Institute of Biomedical Research of Barcelona (IIBB-CSIC) has identified a new therapeutic target for the treatment of abdominal aortic aneurysm (AAA), a degenerative vascular disease with high mortality and no effective pharmacological options.
The study, published in the journal Biomedicine & Pharmacotherapy, reveals how the enzyme ATP-citrate lyase (ACLY) contributes to the development of AAA. The findings show that inhibition of this enzyme with bempedoic acid—a drug used to lower high cholesterol—reduces inflammation and provides protection against the formation of abdominal aortic aneurysm in an experimental model.
The research was led by Dr Cristina Rodríguez Sinovas, head of the Cardiovascular Remodelling Regulatory Mechanisms research group at IR Sant Pau, and Dr José Martínez-González from IIBB-CSIC, both researchers in the Cardiovascular Diseases area of CIBER (CIBERCV).
AAA mainly affects men over the age of 65, with an estimated prevalence of between 4% and 8%. The prevalence in women is significantly lower (around 1% to 2%), but the risk of aortic rupture is higher, and they also have a worse prognosis following surgery.
This disease is characterised by exacerbated inflammation and destructive remodelling of the arterial wall. Currently, the only therapeutic option is surgical intervention in high-risk cases, highlighting the need for alternative strategies.
In this study, samples from AAA patients were analysed, and research was conducted on inflammatory cell cultures and a preclinical mouse model of the disease. “The results show the strong induction of the active form of ACLY in the inflammatory infiltrate of the human aneurysm and how the administration of bempedoic acid in an experimental mouse model improves survival, limits the disorganisation and rupture of elastic fibres in the vascular wall, and attenuates both local and systemic inflammatory responses,” explains Dr Rodríguez Sinovas, coordinator of the study.
“The study highlights the contribution of ACLY in AAA and suggests the potential of repurposing bempedoic acid for the management of these patients, while also laying the groundwork for future clinical trials to assess the potential benefits of this drug in AAA,” concludes Dr Lidia Puertas-Umbert, the study’s first author and a researcher at CIBER and IIBB-CSIC.
The study also involved the collaboration of CIBER research groups from the areas of Cardiovascular Diseases and the Pathophysiology of Obesity and Nutrition, based at the Vall d’Hebron Research Institute and the University of Barcelona.
Puertas-Umbert L, Alonso J, Blanco-Casoliva L, Almendra-Pegueros R, Camacho M, Rodríguez-Sinovas A, Galán M, Roglans N, Laguna JC, Martínez-González J, Rodríguez C. Inhibition of ATP-citrate lyase by bempedoic acid protects against abdominal aortic aneurysm formation in mice. Biomed Pharmacother 2025;184:117876. https://doi.org/10.1016/j.biopha.2025.117876.
