Researchers from the Institute of Biomedical Research of Barcelona (IIBB-CSIC) and the Sant Pau Research Institute (IR Sant Pau), led by Dr Vicenta Llorente Cortes, in collaboration with teams from the CIBER areas of Cardiovascular Diseases (CIBERCV) and Diabetes and Associated Metabolic Diseases (CIBERDEM), have developed peptides that inhibit the aggregation of LDL cholesterol (low-density lipoproteins), thereby preventing the formation of atherosclerotic plaques in an experimental model of hypercholesterolaemia.
The study, recently published in the journal Atherosclerosis, also involved teams from Miguel Servet Hospital in Zaragoza and the University of Basilicata in Italy.
Atherosclerosis, one of the leading causes of heart attacks and strokes, is triggered by the accumulation of LDL cholesterol in the arterial walls. Once trapped in the arterial wall, LDL particles undergo modifications that promote the progression of plaques, which can rupture and obstruct normal blood flow by inducing the formation of clots responsible for acute myocardial infarction.
These newly developed peptides represent a promising and innovative advance in the treatment of this disease. Their potential is especially significant for patients genetically predisposed to atherosclerosis, such as those with familial hypercholesterolaemia, for whom current therapeutic options are limited and insufficient to reduce cardiovascular risk. This underscores the urgent need for new solutions.
As explained by Dr Vicenta Llorente Cortes, who leads the Lipids and Cardiovascular Pathology research group at IIBB-CSIC, “In this study, we developed peptides that bind to and stabilise the structure of LDL particles. Furthermore, in a humanised murine model for lipoproteins, we demonstrated that administering these peptides inhibits atherosclerosis by preserving the structural integrity of LDL.”
This effect, Dr Llorente elaborates, is achieved by stabilising the conformation of ApoB100, a protein found in LDL particles that is crucial for maintaining their integrity and preventing their modification within the arteries. “We also demonstrated the efficacy of this treatment in LDL samples isolated from patients with familial hypercholesterolaemia,” she adds.
The relevance of this entirely novel treatment lies in its unique ability to stabilise the structure of ApoB100 and preserve the integrity of LDL particles in the vascular wall, preventing their aggregation—a key process in the development of atherosclerosis.
Reference Article:
Benitez-Amaro, A., Garcia, E., La Chica Lhoëst, M. T., Martínez, A., Borràs, C., Tondo, M., … Llorente-Cortés, V. (2024). Targeting LDL aggregation decreases atherosclerotic lipid burden in a humanised mouse model of familial hypercholesterolaemia: Crucial role of ApoB100 conformational stabilisation. Atherosclerosis, (118630), 118630. doi:10.1016/j.atherosclerosis.2024.118630
