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NIH Study Uncovers Breakthrough Insights on ‘Bad’ Cholesterol’s Role in the Body

NIH Research Unveils New Insights into How “Bad” Cholesterol ⁣Functions in ‍the Body

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.

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Cryo-electron microscopy‌ image showing ⁤LDL binding to LDLR. ​(Credit: NIH)

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.





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