Osteopontin Identified as a Potential Therapeutic Target to Slow Abdominal Aortic Aneurysm Progression

Although abdominal aortic aneurysm (AAA) can have fatal consequences, there are still no specific pharmacological treatments capable of slowing its progression. Now, a collaborative study involving the Cardiovascular Diseases area of CIBER (CIBERCV), the Barcelona Institute for Biomedical Research-CSIC, and the Sant Pau Research Institude (IR Sant Pau) has identified osteopontin as a protein involved in inflammation and changes affecting the arterial wall, opening new avenues of research into this disease.

The research, led by Dr. José Martínez-González and Dr. Cristina Rodríguez, has demonstrated that blocking this protein reduces aneurysm development in an experimental mouse model, suggesting its potential as a future therapeutic target.

AAA is characterized by the progressive dilation of the aorta, the body's main artery. As the condition progresses, it can lead to rupture of the arterial wall, a potentially fatal complication. Therefore, gaining a more profound understanding of the mechanisms involved in its development is essential for identifying new therapeutic strategies.

The study, published in Translational Research, examines the role of the nuclear receptor NOR-1 in the early stages of aneurysm development. Through gene expression analyses, human tissue samples, and experiments in transgenic mice, the research team has demonstrated that NOR-1 promotes changes associated with inflammation and vascular wall remodeling.

Among the genes identified, SPP1, which encodes osteopontin, stands out. “Studies in human samples showed a correlation between NOR-1 and SPP1 expression, while functional experiments confirmed that NOR-1 regulates SPP1 expression. Data analysis also identified this protein as a link between vascular inflammation and alterations in the extracellular matrix,” explains Dr. Paula Vázquez-Sufuentes, first author of the study and a member of the same research team.

One of the study's main findings is that pharmacological inhibition of osteopontin using the compound HY-146064 reduced the development of angiotensin II-induced aneurysms in transgenic mice. This effect was accompanied by reductions in inflammation, oxidative stress, and vascular remodeling.

“Although the results are promising, further studies will be needed to determine whether osteopontin inhibition could become an effective therapeutic strategy for patients with abdominal aortic aneurysm,” the research team concludes.

Article Reference:

Vázquez-Sufuentes P, Alonso J, Almendra-Pegueros R, Ballester-Servera C, García-Aranda J, Martín-Fernández L, Corrales I, Nus M, Jiménez-Altayó F, Vidal F, Rodríguez C, Martínez-González J. The NOR-1/SPP1/OPN axis as a driver of abdominal aortic aneurysm. Transl Res 2026;298:28–41. https://doi.org/10.1016/j.trsl.2026.09.017.