Science Current Events | Science News | Brightsurf.com
 

How good cholesterol turns bad

February 22, 2012
Researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) have found new evidence to explain how cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol from "good" high density lipoproteins (HDLs) to "bad" low density lipoproteins (LDLs). These findings point the way to the design of safer, more effective next generation CETP inhibitors that could help prevent the development of heart disease.

Gang Ren, a materials physicist and electron microscopy expert with Berkeley Lab's Molecular Foundry, a DOE nanoscience research center, led a study in which the first structural images of CETP interacting with HDLs and LDLs were recorded. The images and structural analyses support the hypothesis that cholesterol is transferred from HDLs to LDLs via a tunnel running through the center of the CETP molecule.

"Our images show that CETP is a small (53 kilodaltons) banana-shaped asymmetric molecule with a tapered N-terminal domain and a globular C-terminal domain," Ren says. "We discovered that the CETP's N-terminal penetrates HDL and its C-terminal interacts with LDL forming a ternary complex. Structure analyses lead us to hypothesize that the interaction may generate molecular forces that twist the terminals, creating pores at both ends of the CETP. These pores connect with central cavities in the CETP to form a tunnel that serves as a conduit for the movement of cholesterol from the HDL."

Ren reports the results of this study in a paper in the journal Nature Chemical Biology titled "Structure basis of transfer between lipoproteins by cholesteryl ester transfer protein." Co-authoring this paper were Lei Zhang, Feng Yan, Shengli Zhang, Dongsheng Lei, M. Arthur Charles, Giorgio Cavigiolio, Michael Oda, Ronald Krauss, Karl Weisgraber, Kerry-Anne Rye, Henry Powna and Xiayang Qiu.

Cardiovascular or heart disease, mainly atherosclerosis, remains the leading cause of death in the United States and throughout the world. Elevated levels of LDL cholesterol and/or reduced levels of HDL cholesterol in human plasma are major risk factors for heart disease. Since CETP activity can reduce HDL-cholesterol concentrations and CETP deficiency is associated with elevated HDL-cholesterol levels, CETP inhibitors have become a highly sought-after pharmacological target for the treatment of heart disease. However, despite this intense clinical interest in CETP, little is known concerning the molecular mechanisms of CETP-mediated cholesterol transfers among lipoproteins, or even how CETP interacts with and binds to lipoproteins.

"It has been very difficult to investigate CETP mechanisms using conventional structural imaging methods because interaction with CETP can alter the size, shape and composition of lipoproteins, especially HDL," Ren says. "We were successful because we used our optimized negative-staining electron microscopy protocol that allows us to flash-fix the structure and efficiently screen more than 300 samples prepared under different conditions."

Ren and his colleagues used their optimized negative-staining electron microscopy protocol to image CETP as it interacted with spherical HDL and LDL particles. Image processing techniques yielded three-dimensional reconstructions of CETP and CETP-bound HDL. Molecular dynamic simulations were used to assess CETP molecular mobility and predict the changes that would be associated with cholesterol transfer. CETP antibodies were used to identify the CEPT interaction domains and validate the cholesterol transfer model by inhibiting CETP. This model presents inviting new targets for future CETP inhibitors.

"Our model identifies new interfaces of CETP that interact with HDL and LDL and delineates the mechanism by which the transfer of cholesterol takes place," Ren says. "This is an important step toward the rational design of next generation CETP inhibitors for treating cardiovascular disease."

###

This research was supported in part by the DOE Office of Science, and in part by W. M. Keck foundations, the Chinese Ministry of Education, the National Institutes of Health, and the Tobacco Related Disease Research Program of California.

Lawrence Berkeley National Laboratory addresses the world's most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab's scientific expertise has been recognized with 13 Nobel prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy's Office of Science. For more, visit www.lbl.gov.

DOE's Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov.

The Molecular Foundry is one of five DOE Nanoscale Science Research Centers (NSRCs), national user facilities for interdisciplinary research at the nanoscale, supported by the DOE Office of Science. Together the NSRCs comprise a suite of complementary facilities that provide researchers with state-of-the-art capabilities to fabricate, process, characterize and model nanoscale materials, and constitute the largest infrastructure investment of the National Nanotechnology Initiative. The NSRCs are located at DOE's Argonne, Brookhaven, Lawrence Berkeley, Oak Ridge and Sandia and Los Alamos National Laboratories. For more information about the DOE NSRCs, please visit http://science.energy.gov

DOE/Lawrence Berkeley National Laboratory


Related Cholesterol Current Events and Cholesterol News Articles


Protein may improve liver regeneration
Researchers at UC Davis have illuminated an important distinction between mice and humans: how human livers heal.

To statin or not to statin?
Cholesterol-lowering statins have transformed the treatment of heart disease. But while the decision to use the drugs in patients with a history of heart attacks and strokes is mostly clear-cut, that choice can be a far trickier proposition for the tens of millions of Americans with high cholesterol but no overt disease.

New scientific review suggests some women may benefit from considering use of S-equol to ease menopause symptoms
The investigational S-equol nutritional supplement may be a viable agent to alleviate certain menopause symptoms, such as hot flashes, according to a new peer-reviewed article in the March Journal of Women's Health.

Study: Increased dietary magnesium intake associated with improved diabetes-related health outcomes
A recent analysis published in the Journal of Human Nutrition & Food Science reveals a beneficial relationship between dietary magnesium intake and diabetes-related outcomes including decreased risk for metabolic syndrome, obesity or overweight, elevated blood pressure, and reduced HDL (good) cholesterol.

New findings support the benefits of eating walnuts on overall health
Multiple new research abstracts suggest walnuts may have the potential to positively affect several important health factors. From their impact on colon cancer and certain aspects of cognitive aging, to their positive effect on both gut health and vascular health, the research findings presented at Experimental Biology 2015 (EB) detail our latest understanding of walnuts' inner workings.

Vitamin D helps immune cells prevent atherosclerosis and diabetes
Altered signaling through the vitamin D receptor on certain immune cells may play a role in causing the chronic inflammation that leads to cardiometabolic disease, the combination of type 2 diabetes and heart disease that is the most common cause of illness and death in Western populations.

Vitamin D prevents diabetes and clogged arteries in mice
In recent years, a deficiency of vitamin D has been linked to type 2 diabetes and heart disease, two illnesses that commonly occur together and are the most common cause of illness and death in Western countries.

Serious risks from common IV devices mean doctors should choose carefully, U-M experts say
Every day, patients around the country get IV devices placed in their arms, to make it easier to receive medicines or have blood drawn over the course of days or weeks. But these PICC lines, as they're called, also raise the risk of potentially dangerous blood clots.

Cardiometabolic risk factors harden arteries early in Mexican-Americans
Cardiometabolic risk factors, such as high blood pressure and elevated blood sugar, appear to have a bigger effect than obesity on hardening arteries early among Mexican-Americans, according to research in the Journal of the American Heart Association.

Healthy diet reduces risk of cardiovascular disease by a third in over-40s
Men and women who adapt their daily diet to meet current UK dietary guidelines could reduce their risk of a heart attack or a stroke by up to a third, according to a new study by King's College London.
More Cholesterol Current Events and Cholesterol News Articles

The Great Cholesterol Myth: Why Lowering Your Cholesterol Won't Prevent Heart Disease-and the Statin-Free Plan That Will

The Great Cholesterol Myth: Why Lowering Your Cholesterol Won't Prevent Heart Disease-and the Statin-Free Plan That Will
by Jonny Bowden (Author), Stephen Sinatra (Author)


Heart disease is the #1 killer. However, traditional heart disease protocols--with their emphasis on lowering cholesterol--have it all wrong. Emerging science is showing that cholesterol levels are a poor predictor of heart disease and that standard prescriptions for lowering it, such as ineffective low-fat/high-carb diets and serious, side-effect-causing statin drugs, obscure the real causes of heart disease. Even doctors at leading institutions have been misled for years based on creative reporting of research results from pharmaceutical companies intent on supporting the $31-billion-a-year cholesterol-lowering drug industry.The Great Cholesterol Myth reveals the real culprits of heart disease, including:
Inflammation
Fibrinogen
Triglycerides
Homocysteine
Belly...

Cholesterol Down: Ten Simple Steps to Lower Your Cholesterol in Four Weeks--Without Prescription Drugs

Cholesterol Down: Ten Simple Steps to Lower Your Cholesterol in Four Weeks--Without Prescription Drugs
by Janet Brill (Author)


Take Control of Your Cholesterol— Without Drugs

If you are one of the nearly 100 million Americans struggling with high cholesterol, then Dr. Janet Brill offers you a revolutionary new plan for taking control of your health—without the risks of statin drugs. With Dr. Brill’s breakthrough Cholesterol Down Plan, you simply add nine “miracle foods” to your regular diet and thirty minutes of walking to your daily routine. That’s all. This straightforward and easy-to-follow program can lower your LDL (“bad”) cholesterol by as much as 47 percent in just four weeks.

Cholesterol Down explains Dr. Brill’s ten-point plan as well as the science behind it. You’ll learn how each miracle food affects LDL cholesterol and how the foods work together for maximum effect,...

Cholesterol: Low Cholesterol Diet Solutions - A Proven Guide On How To Lower Your Cholesterol Naturally!: Cholesterol and Cholesterol Diet (Cholesterol and Low Cholesterol Diet Book 1)

Cholesterol: Low Cholesterol Diet Solutions - A Proven Guide On How To Lower Your Cholesterol Naturally!: Cholesterol and Cholesterol Diet (Cholesterol and Low Cholesterol Diet Book 1)


Take action today and lower your cholesterol level drastically !

I want to congratulate you. The fact that you are reading this book description tells me that you are going to invest into one of the most important areas of your life: your health.

Everyone knows that it's important to pay attention to your diet - Yet most of us don't. In the busy world that we live in, more often than not we do not take the time to think consciously about what we are putting into our bodies: fast and processed foods, fatty meats, highly refined carbohydrates. This leads to a cholesterol level that can get out of control. Often times people do not take action to improve their health until they have concrete problems, such as diabetes, cancer, stroke, heart diseases.

The Cholesterol Solution Guide: Lower Your Cholesterol in 30 Days Without Drugs

The Cholesterol Solution Guide: Lower Your Cholesterol in 30 Days Without Drugs
by Michael E. Reese (Author)


Discover How Easy It Is To Lower Your Cholesterol in 30 DAYS This book will tell you what cholesterol is, its signs, symptoms, causes, and types, so that you will be aware of the need to reduce your LDL or bad cholesterol levels and increase the HDL or good cholesterol levels. This book contains proven steps and strategies on how to lower your cholesterol the natural way in just 30 days. ORDER Your Copy Today!

Cholesterol: Natural Remedies To Lower Cholesterol - Lower Your Cholesterol Naturally Without Drugs! (Diabetes, Herbal Remedies, Honey, Coconut Oil, Diabetes ... Apple Cider Vinegar, Cholesterol Myth)

Cholesterol: Natural Remedies To Lower Cholesterol - Lower Your Cholesterol Naturally Without Drugs! (Diabetes, Herbal Remedies, Honey, Coconut Oil, Diabetes ... Apple Cider Vinegar, Cholesterol Myth)


This "Cholesterol" book contains proven steps and strategies on how to Find and apply the best natural remedies to lower high blood cholesterol when you let go of prevailing myths.Today only, get this Amazing Amazon book for this incredibly discounted price! Read on your PC, Mac, Smart Phone, Tablet or Kindle Device. In this book, you will also find proven steps on how to appreciate the value of natural solutions in treating your high blood cholesterol instead of depending on the usual drug-based medications.These and more await you.Here Is A Preview Of What You'll Learn... Debunking These Cholesterol Myths Will Change How To Approach Your Condition3 Important Reasons You Should Lower Cholesterol Naturally Without Drugs Understanding The Connection Between Diabetes And High Cholesterol...

Cholesterol Clarity: What The HDL Is Wrong With My Numbers?

Cholesterol Clarity: What The HDL Is Wrong With My Numbers?
by Jimmy Moore (Author), Eric C. Westman (Author)


Are you confused by what your cholesterol levels really say about your health?

Don't you wish someone could just spell it out in simple, easy-to-understand language and tell you what, if anything, you need to do about your cholesterol? Good news! That's precisely what Cholesterol Clarity is designed to do. Jimmy Moore, a prominent and highly respected health blogger and podcaster, has teamed up with Dr. Eric Westman, a practicing internist and nutrition researcher, to bring you one of the most unique books you'll ever read on this subject, featuring exclusive interviews with twenty-nine of the world's top experts from various fields to give you the complete lowdown on cholesterol. If you're worried about any confusing medical jargon in this book, don't be—this critical...

Cholesterol is Not the Culprit: A Guide to Preventing Heart Disease

Cholesterol is Not the Culprit: A Guide to Preventing Heart Disease
by Dr Fred Kummerow (Author)


You will find a lot in this book related to diet and heart disease; it is the number one cause of death in the U.S. and throughout much of the world and also the focus of the majority of my career. To me, researching diet and heart disease is like being the detective in a good mystery book who follows clue after clue and finally comes up with an unexpected answer. The detective is always trying to find out who and what killed the person. Some detectives view cholesterol as the killer in heart disease, but I show you why that's not so. I hope in reading this book, you'll not only learn what is healthy to eat, but also why it is healthy to do so. How the body uses food to make what we need to keep going is an incredible, almost magical, process. We, as well as all animals and plants, are...

Heart Health: 101 Best Foods To Lower Cholesterol and Prevent Heart Disease

Heart Health: 101 Best Foods To Lower Cholesterol and Prevent Heart Disease
by Millwood Media


Don’t be the next statistic!

Heart disease is the leading cause of death in the United States and is a major cause of disability!

While it’s important to always be paying attention to your calorie intake in order to achieve a healthy body weight, one cannot overlook where these calories are coming from. If you eat a diet that is full of fatty meats, highly refined carbohydrates, and other fast and processed foods, you’re setting yourself up for numerous health problems.

Some of the main health conditions that you could be at risk for include cancer, diabetes, stroke, as well as heart disease. If you let your cholesterol levels get out of check and are experiencing high blood pressure or other factors due to that, you could be at risk for one...

American Heart Association Low-Fat, Low-Cholesterol Cookbook, 4th edition: Delicious Recipes to Help Lower Your Cholesterol

American Heart Association Low-Fat, Low-Cholesterol Cookbook, 4th edition: Delicious Recipes to Help Lower Your Cholesterol
by American Heart Association (Author)


Eat wisely, eat well.

The nation’s most trusted authority on heart-healthy living presents the fourth edition of this classic cookbook, with the most up-to-date information on heart health and nutrition—including the effects of saturated and trans fats and cholesterol—and 50 exciting new recipes.

American Heart Association Low-Fat, Low-Cholesterol Cookbook offers more than 200 delicious, easy-to-prepare dishes, including:

•Fresh Basil and Kalamata Hummus
•Elegant Beef Tenderloin
•Tilapia Tacos with Fresh Salsa
•Garlic Chicken Fillets in Balsamic Vinegar
•Peppery Beef with Blue Cheese Sauce
•Thai Coconut Curry with Vegetables
•Sweet Potatoes in Creamy Cinnamon Sauce
•Pumpkin-Pie Coffeecake
•Streusel-Topped Blueberry...

The Truth About Statins: Risks and Alternatives to Cholesterol-Lowering Drugs

The Truth About Statins: Risks and Alternatives to Cholesterol-Lowering Drugs
by Barbara H. Roberts M.D. (Author)


COULD STATIN DRUGS ACTUALLY HARM YOU?

Despite the rosy picture painted in the ads of a miracle cure for high cholesterol and its attendant heart disease, the reality of taking statins may be far less pretty. Dr. Barbara H. Roberts, director of the Women’s Cardiac Center at the Miriam Hospital in Rhode Island, discusses both the benefits and health risks of these popular drugs in this comprehensive guide that finally reveals the questionable science behind the research studies. This honest, patient-friendly appraisal of the most widely used medications in the world may shock you, but it may also save your life.

Offering clear-cut, easy-to-understand information in an easily accessible fashion, Dr. Roberts explains how to take the best possible care of your heart,...

© 2015 BrightSurf.com