Therapy developed to restore heart damage caused by cholesterol

A team of researchers from the University of California (United States) and the University of Toulouse (France) discovered how cholesterol can alter the internal functioning of the heart and developed an experimental immunotherapy capable of reversing this process.

The study, published in the Journal of Lipid Research, was led by Vicenta Llorente-Cortés, a researcher from the Lipids and Cardiovascular Pathology group at the Barcelona Institute for Biomedical Research of the CSIC (IIBB-CSIC), the Sant Pau Research Institute (IR Sant Pau), and the CIBERCV (Central European Research Council).

As explained in a statement by the Sant Pau Research Institute on Wednesday, cholesterol, when it accumulates in the mitochondria of cardiomyocytes (heart muscle cells), can affect the internal functioning of the heart.

This organ requires a high and constant supply of energy and depends on the efficiency of mitochondria, the structures within cells that function as energy centers, to maintain continuous muscle contraction.

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"We have demonstrated a previously unknown mechanism: cholesterol transported by lipoproteins not only affects blood vessels or deposits in plaques, but also penetrates the heart's mitochondria, compromising cellular respiration and, consequently, the function of the heart itself," Llorente-Cortés explained.

In this regard, various studies have indicated that, "in altered metabolic conditions, such as obesity, diabetes or hypercholesterolemia , progressive mitochondrial dysfunction occurs that aggravates heart failure ."

To address this damaging mechanism, the team developed an experimental immunotherapy based on "monoclonal antibodies " that selectively blocks the LRP1 receptor from transferring cholesterol esters, transported in the blood by lipoproteins, into the cell interior, thereby halting their accumulation in mitochondria.

"Our experimental treatment allows us to act on the heart at a level previously untouched: within the cell, within the mitochondria, where the vital energy of the heart muscle is generated," Llorente-Cortés noted.

This study also included collaboration with researchers from CIBERdem, the Barcelona Institute of Molecular Biology of the CSIC (IBMB-CSIC), the University of Barcelona (UB), the Autonomous University of Barcelona (UAB), the University of California (USA) and the University of Toulouse (France).

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