NIH Research Unveils New Insights into How “Bad” Cholesterol Functions in the Body
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Wednesday, December 11, 2024 – A groundbreaking study by scientists at the National Institutes of Health (NIH) has shed new light on the mechanisms of low-density lipoprotein cholesterol (LDL-C), commonly known as “bad” cholesterol. The findings, published in Nature, could pave the way for more personalized treatments for cardiovascular disease, the leading cause of death worldwide.
The research team, led by Dr. Alan Remaley and Dr. Joseph Marcotrigiano, has for the first time visualized how the main structural protein of LDL binds to its receptor, a process that initiates the removal of LDL from the bloodstream. This discovery provides critical insights into how LDL contributes to heart disease and could lead to more effective treatments for high cholesterol.
“LDL is one of the main drivers of cardiovascular disease which kills one person every 33 seconds, so if you want to understand your enemy, you want to know what it looks like,” said dr. Alan Remaley, co-senior author of the study and head of the Lipoprotein metabolism Laboratory at NIH’s National Heart, Lung, and Blood Institute.
Until now, scientists have struggled to fully understand the structure of LDL and its interaction with the LDL receptor (LDLR). Typically, when LDL binds to LDLR, the body begins the process of clearing LDL from the blood. However, genetic mutations can disrupt this process, causing LDL to accumulate in the blood and form plaque in the arteries, leading to atherosclerosis and increasing the risk of heart disease.
Using advanced cryo-electron microscopy and artificial intelligence-driven protein prediction software, the researchers were able to capture high-resolution images of LDL binding to LDLR. This technology allowed them to identify genetic mutations associated with high LDL levels and understand how these mutations affect the binding process.
“LDL is enormous and varies in size, making it very complex,” explained Dr. Joseph Marcotrigiano, chief of the Structural Virology Section at NIH’s National Institute of allergy and Infectious Diseases and co-senior author of the study. “No one’s ever gotten to the resolution we have. We could see so much detail and start to tease apart how it works in the body.”
The study revealed that many of the genetic mutations associated with familial hypercholesterolemia (FH), a hereditary condition characterized by extremely high LDL levels, cluster in specific regions of LDL. This discovery could lead to the development of targeted therapies for FH and other forms of high cholesterol.
Moreover, the findings could enhance the effectiveness of existing treatments like statins, which lower LDL by increasing LDLR in cells. By understanding the precise mechanisms of LDL binding, researchers may be able to design new drugs that more effectively reduce LDL levels in the blood.
The research was funded by the Intramural Research Programs of the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases. The use of AI-driven protein prediction software, developed by researchers who were recently awarded the 2024 Nobel Prize in Chemistry, played a crucial role in the study’s success.
These groundbreaking insights into the workings of “bad” cholesterol could revolutionize the treatment of cardiovascular disease, offering hope for more personalized and effective therapies in the future.
For more information, visit the National institutes of health website.
Revolutionary Discovery: Unlocking the Secrets of Heart Disease Prevention
In a groundbreaking study, researchers from the National Institutes of Health (NIH) have unveiled the intricate structure of Apolipoprotein B100 bound to the low-density lipoprotein receptor. This discovery,published in Nature in 2024,promises to revolutionize our understanding of heart disease and pave the way for more effective treatments.
The Science Behind the Breakthrough
The study, led by Dr.Reimund M and colleagues, provides a detailed molecular blueprint of how Apolipoprotein B100 interacts with the low-density lipoprotein (LDL) receptor. This interaction is crucial in the development of atherosclerosis, the leading cause of heart disease. By mapping these structures, researchers can now identify new targets for therapeutic interventions.
“This research opens up new avenues for developing drugs that can prevent the binding of Apolipoprotein B100 to the LDL receptor, potentially reducing the risk of heart disease,” said Dr. Reimund M.
the findings are a significant leap forward in the fight against heart disease, which remains the leading cause of death in the United States. The study was conducted in collaboration with the National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the High-Value Datasets program from the NIH Office of data Science Strategy.
Implications for Public Health
The implications of this research are vast. By understanding the molecular mechanisms at play, scientists can design more targeted and effective treatments. This could lead to a future where heart disease is not only better managed but potentially prevented altogether.
Dr. Dearborn AD, another key researcher in the study, emphasized the importance of this discovery: “This is not just about treating symptoms; it’s about addressing the root causes of heart disease. Our findings could lead to a paradigm shift in how we approach cardiovascular health.”
About the NIH and NHLBI
The National Institutes of Health (NIH) is the nation’s premier medical research agency, comprising 27 Institutes and Centers. As a part of the U.S. Department of Health and Human Services, NIH is dedicated to conducting and supporting research that advances scientific knowledge and improves public health.
The National Heart, Lung, and Blood Institute (NHLBI), a leading component of NIH, has been at the forefront of research in heart, lung, and blood diseases and sleep disorders. Their work has saved countless lives and continues to drive innovation in medical science.
For more information, visit www.nih.gov and www.nhlbi.nih.gov.
Reference
Reimund M, Dearborn AD, Graziano G, et al. Structure of Apolipoprotein B100 bound to low-density lipoprotein receptor. Nature. 2024. DOI: 10.1038/s41586-024-08223-0
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Revolutionary Discovery: Unlocking the Secrets of Heart Disease Prevention
In a groundbreaking study, researchers from the National Institutes of Health (NIH) have unveiled the intricate structure of Apolipoprotein B100 bound to the low-density lipoprotein receptor. This discovery, published in Nature in 2024, promises to revolutionize our understanding of heart disease and pave the way for more effective treatments.
Interview with Dr. Alan Remaley and Dr. Joseph Marcotrigiano
Senior Editor: Thank you both for joining us today. Your recent study in Nature has made headlines worldwide. Can you start by explaining what this research means for the field of cardiovascular medicine?
Dr. Alan Remaley: Absolutely. This study is a significant step forward in understanding how LDL, or ”bad” cholesterol, interacts with its receptor in the body. By visualizing this process at a molecular level,we can now identify specific genetic mutations that contribute to high LDL levels and develop targeted therapies to address them.
dr. Joseph Marcotrigiano: Yes, and what’s particularly exciting is that this research opens the door to more personalized treatments.By understanding the precise mechanisms of LDL binding, we can design drugs that are more effective in reducing LDL levels, which is crucial for preventing heart disease.
The Role of Advanced Technology
Senior Editor: The study mentions the use of advanced cryo-electron microscopy and AI-driven protein prediction software. How did these technologies contribute to your findings?
Dr. Remaley: cryo-electron microscopy allowed us to capture high-resolution images of LDL binding to its receptor. This technology was essential because LDL is a large and complex molecule, and traditional methods couldn’t provide the level of detail we needed.
Dr. Marcotrigiano: The AI-driven protein prediction software was also crucial.It helped us identify genetic mutations associated with high LDL levels and understand how these mutations affect the binding process. Without this technology, we wouldn’t have been able to tease apart the intricate details of LDL’s function in the body.
implications for Treatment
Senior Editor: What are the potential implications of this research for treating high cholesterol and heart disease?
Dr. Remaley: One of the most exciting possibilities is the advancement of targeted therapies for familial hypercholesterolemia (FH) and other forms of high cholesterol. By identifying specific genetic mutations, we can create treatments that are more effective for individuals with these conditions.
Dr. Marcotrigiano: Additionally, this research could enhance the effectiveness of existing treatments like statins. By understanding the precise mechanisms of LDL binding, we may be able to design new drugs that work more effectively in reducing LDL levels, ultimately preventing heart disease.
The Future of Cardiovascular Research
Senior editor: Looking ahead,what does this discovery mean for the future of cardiovascular research?
Dr. Remaley: This study is just the beginning. we now have a clearer picture of how LDL works in the body, but there’s still much to learn. Future research will focus on developing and testing new treatments based on these findings.
Dr. Marcotrigiano: Yes, and I believe this research will inspire further advancements in the field. By continuing to explore the complexities of LDL and its receptor, we can unlock even more secrets of heart disease prevention and treatment.
Senior Editor: Thank you both for sharing your insights. This research is truly groundbreaking and offers hope for a future with fewer heart disease-related deaths.
For more facts, visit the National Institutes of Health website.
