An international team of researchers has uncovered a groundbreaking discovery in the fight against heart disease.
They found that cholesterol does not just affect blood vessels and create harmful plaques—it can also sneak into the heart’s energy factories, known as mitochondria, and cause serious damage.
Even more promising, the team developed an experimental immunotherapy that can reverse this damage, restoring the heart’s ability to produce energy and function properly.
This study, led by Dr. Vicenta Llorente-Cortés from the Institute of Biomedical Research of Barcelona (IIBB-CSIC), was recently published in the Journal of Lipid Research.
The heart is one of the most energy-demanding organs in the body. It relies on a constant supply of energy to keep pumping blood throughout our lives.
To do this, heart cells, called cardiomyocytes, are packed with mitochondria—tiny structures that turn nutrients into energy.
In fact, mitochondria make up about one-third of each heart cell’s volume. These powerful energy producers use a process called oxidative phosphorylation to generate ATP, the molecule that fuels heart contractions.
But when cholesterol starts building up inside the heart cells, it disrupts this energy production. The study identified that cholesterol, in the form of cholesteryl esters, accumulates inside the mitochondria of heart cells. This build-up happens through a specific pathway: the LRP1 receptor, a protein on the surface of heart cells.
This receptor allows cholesterol carried by lipoproteins to enter the cell. Under conditions like obesity, diabetes, or high cholesterol levels, this process speeds up, and more cholesterol finds its way into the mitochondria. Over time, it damages the structure of these tiny powerhouses, blocking their ability to produce energy effectively.
Dr. Llorente-Cortés explained that this finding reveals a new and dangerous way cholesterol harms the heart. “We have shown that cholesterol doesn’t just clog arteries—it can also get inside the heart’s mitochondria, stopping them from making energy. This weakens the heart and leads to heart failure.”
To solve this problem, the research team created a unique type of immunotherapy. This new treatment uses monoclonal antibodies designed to target the P3 domain of the LRP1 receptor. By blocking this specific part of the receptor, the therapy prevents cholesterol from entering the mitochondria, stopping the damage before it happens.
To test their new treatment, the team worked with a rabbit model that mimics the cholesterol profiles seen in humans. Using advanced techniques like bioenergetics analysis, mass spectrometry, and electron microscopy, they measured how well the heart cells produced energy before and after the treatment.
What they found was astonishing: after using the anti-P3 antibodies, cholesterol levels in the mitochondria dropped, and the structure of the mitochondria improved dramatically. Even the folds inside mitochondria, called cristae—which are crucial for energy production—were restored to their healthy state.
The therapy also boosted the efficiency of oxidative phosphorylation, leading to better ATP production. ATP is the main energy currency for cells, and its restoration is key to maintaining heart function.
The researchers noted another interesting benefit: the treatment improved the interaction between mitochondria and lipid droplets within the cell. This helps balance fat storage and energy production, further supporting heart health.
Dr. Llorente-Cortés described the therapy as a completely new way of treating heart conditions linked to cholesterol. “Our experimental treatment allows us to act on the heart at a level that had not been targeted before: inside the cell, inside the mitochondria, where the vital energy of the cardiac muscle is generated.”
This research opens the door to a potential new treatment for heart failure and other heart diseases linked to cholesterol, such as obesity-related heart problems and myocardial ischemia.
Current heart disease treatments mostly focus on controlling blood pressure, reducing cholesterol in the blood, and managing symptoms. However, there has never been a direct approach to fix the damage cholesterol does inside the heart cells themselves—until now.
The study addresses an important gap in heart disease treatment: the lack of therapies that protect the mitochondria from cholesterol-induced damage. Cardiovascular diseases are responsible for one in three deaths worldwide, and while modern medicine has improved survival rates, many patients still suffer from long-term heart damage.
This new immunotherapy could change that by going straight to the root of the problem inside the cells, restoring energy production, and potentially preventing heart failure.
Dr. Llorente-Cortés is optimistic about the future, stating, “This discovery has very clear clinical implications: it enables us to envision new therapies aimed at preserving mitochondrial function in patients with high cardiovascular risk.
This is especially relevant in contexts where circulating cholesterol remains persistently elevated, and lowering it externally is no longer enough—we need to protect the heart from within.”
The next steps for the research team include clinical trials to test the safety and effectiveness of this therapy in humans. If successful, this immunotherapy could become a vital tool in the fight against heart disease, offering new hope to millions of patients worldwide.
If you care about heart health, please read studies about how drinking milk affects risks of heart disease , and herbal supplements could harm your heart rhythm.
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The research findings can be found in Journal of Lipid Research.
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