Possible new treatment against atherosclerosis

Atherosclerosis, one of the leading causes of heart attacks or strokes, is caused by the buildup of LDL (low-density lipoprotein) cholesterol, from the blood, in the wall of the arteries. The low-density lipoproteins accumulated in the wall are modified, favoring the progression of plaques, which can rupture and block normal blood circulation, by inducing the formation of clots that cause acute myocardial infarction.

Scientists have managed to prepare peptides that prevent the aggregation of LDL cholesterol and the formation of atherosclerotic plaques in the arteries.

These scientists are from the Sant Pau Research Institute (IR Sant Pau) in Barcelona, ​​as well as the Barcelona Biomedical Research Institute (IIBB), attached to the Higher Council for Scientific Research (CSIC), the Center for Biomedical Research in Disease Network Cardiovascular (CIBERCV) and the Network Biomedical Research Center for Diabetes and Associated Metabolic Diseases (CIBERDEM), the Miguel Servet Hospital in Zaragoza, in Spain, and the University of Basilicata in Italy.

The research and development team, made up of, among others, Aleyda Benítez Amaro and Vicenta Llorente Cortes, has developed peptides that inhibit the aggregation of LDL cholesterol, preventing the formation of atherosclerotic plaques, in an experimental model of hypercholesterolemia.

These new peptides now developed represent a promising and novel advance in the treatment of this disease. Its potential is especially relevant in patients with a genetic predisposition to suffer atherosclerosis, such as those with familial hypercholesterolemia, for whom current therapeutic options are limited and their effectiveness in inhibiting this disease is insufficient to reduce cardiovascular risk, making the search for new solutions.

As Llorente Cortes, who heads the Lipids and Cardiovascular Pathology research group at the IIBB, explains, “in this study, we have developed peptides that bind and stabilize the structure of LDL particles. Furthermore, in a humanized murine model for lipoproteins, we have shown that the administration of these peptides inhibits atherosclerosis by preserving the structural integrity of LDL.”

This effect, explains Llorente, is achieved through the stabilization of the conformation of ApoB100, a protein found in LDL particles and which is essential for preserving their integrity and preventing their modification in the arteries. Likewise, “we show the effectiveness of this treatment in LDL samples isolated from patients with familial hypercholesterolemia.”

LDL aggregates in an untreated hypercholesterolemic animal (left) compared to (non-aggregated) LDL in an animal treated with the new peptides (right). (Images: IIBB / CSIC)

The relevance of this innovative treatment lies in its unique ability to stabilize 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 arteriosclerosis.

The study is titled “Targeting LDL aggregation decreases atherosclerotic lipid burden in a humanized mouse model of familial hypercholesterolemia: Crucial role of ApoB100 conformational stabilization”. And it has been published in the academic journal Atherosclerosis. (Source: Mercè Fernández / CSIC)