Heterozygous familial hypercholesterolemia is a disease inherited primarily from mutations in the “bad” cholesterol (LDL) receptor gene and is characterized by high levels of cholesterol carried by LDL that are often associated with low levels of “good” cholesterol (HDL). Familial hypercholesterolemia is very common, it is estimated that at least 1 in 250 people are affected by this disease. Among other consequences, the disease carries a high cardiovascular risk.
A new study shows a new therapeutic avenue that could improve the cardioprotective potential of “good” cholesterol (HDL) in people with familial hypercholesterolemia.
The study was carried out by experts from the Sant Pau Research Institute, the Hospital de la Santa Creu i Sant Pau in Barcelona, the Biomedical Research Center of the Network for Diabetes and Associated Metabolic Diseases (CIBERDEM) and the Center for biomedical research of the Cardiovascular Diseases network (CIBERCV), in Spain.
The work was led by Joan Carles Escolà Gil and Francisco Blanco Vaca, CIBERDEM researchers at the Sant Pau Research Institute and the Hospital de la Santa Creu i Sant Pau.
New way to eliminate “bad” cholesterol.
PCSK9 protein inhibitors constitute one of the most advanced and effective treatments for reducing LDL cholesterol levels and, therefore, cardiovascular risk. Now, this study has identified a new metabolic pathway by which these PCSK9 protein inhibitors promote high-density lipoprotein (HDL) to transport cholesterol from macrophages into the arterial wall and transfer it to low-density lipoprotein (LDL), for subsequent elimination from the body through the liver, bile and feces.
The results of the study demonstrate that functional alterations of the LDL receptor decrease the transport of cholesterol from macrophages and its elimination from the body, and that this can be reversed with PCSK9 inhibitors. Carla Borràs, co-author of the study and CIBERDEM researcher at the Sant Pau Research Institute, indicates that: “the results of this new study may open up new therapeutic possibilities to prevent cardiovascular risk in patients by increasing this metabolic pathway”.
Likewise, Marina Canyelles, co-author of the study and member of the same research group, assures that “future research should analyze the effects of PCSK9 inhibitors on this pathway in other forms of hypercholesterolemia and its association with the reduction of cardiovascular events”.
Research personnel responsible for the study. (Photo: CIBER)
Researchers from the Sant Joan de Reus University Hospital, the Biomedical Research Institute of Barcelona, the Ramón y Cajal University Hospital and Finnish institutions such as the Wihuri Research Institute and the Research Institute also participated in the study. doctor of the Minerva Foundation.
The study is titled “PCSK9 Antibody Treatment Specifically Enhances the Macrophage-Specific Reverse Cholesterol Transport Pathway in Heterozygous Familial Hypercholesterolemia.” And it was published in the academic journal JACC: Basic to Translational Science. (Source: CIBER)
What are the latest treatments available for patients with heterozygous familial hypercholesterolemia?
Interview Between Time.news Editor and Dr. Joan Carles Escolà Gil, Cardiovascular Research Expert
Time.news Editor: Thank you for joining us today, Dr. Escolà Gil. To start off, can you give our readers a brief overview of heterozygous familial hypercholesterolemia? Why is it considered such a significant health issue?
Dr. Escolà Gil: Of course! Heterozygous familial hypercholesterolemia is a genetic disorder that primarily results from mutations in the LDL receptor gene. It leads to elevated levels of ”bad” cholesterol, or LDL, which can create a substantial cardiovascular risk for affected individuals. Studies estimate that about 1 in 250 people may be affected, but many remain undiagnosed. This condition significantly increases the chances of heart disease and stroke later in life.
Time.news Editor: That’s alarming, especially considering how common it is. Your recent study suggests a new therapeutic approach for improving the role of “good” cholesterol, or HDL, in patients with this condition. Could you elaborate on what your research found?
Dr. Escolà Gil: Certainly! Our research delves into the effectiveness of PCSK9 protein inhibitors, which have shown promise in significantly lowering LDL cholesterol levels. We discovered a novel metabolic pathway through which these inhibitors can enhance HDL functionality. Basically, they help HDL transport cholesterol from macrophages located in the arterial walls, facilitating the transfer to LDL for eventual elimination through the liver and bile.
Time.news Editor: That sounds like a crucial breakthrough. How does this process of HDL functioning contribute to a decrease in cardiovascular risk?
Dr. Escolà Gil: By enhancing the ability of HDL to transport cholesterol out of the arterial walls, we can reduce the cholesterol buildup that leads to atherosclerosis—a key factor in cardiovascular disease. With effective HDL transport, there’s a dual benefit: lowering the overall levels of “bad” cholesterol and promoting a healthier vascular environment.
Time.news Editor: Given the impact of familial hypercholesterolemia, what implications do you see this study having on treatment protocols moving forward?
Dr. Escolà Gil: Our findings suggest that therapies focusing on both the reduction of LDL and the enhancement of HDL should be integral to managing familial hypercholesterolemia. This could completely reshape treatment strategies and lead to personalized medicine approaches that take into account individual profiles for lipid metabolism.
Time.news Editor: What can patients currently with familial hypercholesterolemia take away from your research? How can they advocate for their health?
Dr. Escolà Gil: Patients should be proactive in discussing their cholesterol levels with their healthcare providers, especially considering how common this condition is yet often goes undiagnosed. Understanding the risks and available treatments, including the potential role of PCSK9 inhibitors and HDL-enhancing strategies, can empower them to make informed decisions about their care. Regular screenings and lifestyle modifications remain crucial as well.
Time.news Editor: It’s evident that your research opens up exciting prospects for tackling this prevalent health issue. What are the next steps for you and your team following this study?
Dr. Escolà Gil: Next, we plan to conduct larger, more comprehensive studies to validate our findings and explore how these treatments can be integrated into existing care frameworks. We’re also looking into collaborations that could aid in translating our research into clinical practice more rapidly.
Time.news Editor: Thank you for your insights, Dr. Escolà Gil. It’s inspiring to see such important research moving forward. We look forward to hearing more about your work in the future.
Dr. Escolà Gil: Thank you for having me! It’s a pleasure to share our findings, and I appreciate your interest in this critical health issue.