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


Lipid testing underutilized in adults taking antipsychotic medications
Too few adults taking antipsychotic medications are being screened for abnormalities in lipids, which include cholesterol and triglycerides, new research from the University of Colorado Anschutz Medical Campus finds.

Telomere length in circulating blood cells does not predict asymptomatic atherosclerosis
Cardiovascular disease (CVD) is the main cause of death in the world, killing 17.5 million people every year according to WHO figures.

Mutation protects against heart disease
According to new international research, just less than one per cent of the population is naturally protected against developing chronic coronary artery diseases.

Can sesame-based ingredients reduce oxidative stress?
The antioxidant boosting properties of sesame, and especially sesame oil, can have a significant effect on oxidative stress, improving human health, according to a systematic review published in Journal of Medicinal Food, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.

Statins may shield unborn babies from mother's stress, study suggests
Statins could protect the hearts of babies in the womb from the adverse effects of their mother's stress, research suggests.

Physical activity is 'magic bullet' for pandemics of obesity and cardiovascular disease
In an editorial published in the current issue of Cardiology, professors from the Charles E. Schmidt College of Medicine at Florida Atlantic University have evaluated the totality of evidence and conclude that regular physical activity bears the closest resemblance to a "magic bullet" to combat the worldwide epidemic of obesity and cardiovascular disease.

New gene for familial high cholesterol
New research from Denmark reveals the gene that explains one quarter of all familial hypercholesterolemia with very high blood cholesterol. Familial hypercholesterolemia is the most common genetic disorder leading to premature death, found in 1 in 200 people.

Fruit discovery could provide new treatments for obesity, type 2 diabetes and cardiovascular disease
A combination of two compounds found in red grapes and oranges could be used to improve the health of people with diabetes, and reduce cases of obesity and heart disease.

UTSA professor Janakiram Seshu explores new method to stop the spread of Lyme disease
Medication that is normally used to lower cholesterol could stop the spread of Lyme disease, according to a new study co-authored by Janakiram Seshu, associate professor of biology at The University of Texas at San Antonio (UTSA).

Videogame addiction: Sleep loss, obesity, and cardiovascular risk for some gamers
Some children and youth with high videogame addiction tendencies may be at risk of sleep deprivation and disorders associated with obesity and poor cardio-metabolic health, Hamilton researchers have found.
More Cholesterol Current Events and Cholesterol News Articles

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,...

The Great Cholesterol Myth Now Includes 100 Recipes for Preventing and Reversing Heart Disease: Why Lowering Your Cholesterol Won't Prevent Heart Disease-and the Statin-Free Plan that Will

The Great Cholesterol Myth Now Includes 100 Recipes for Preventing and Reversing Heart Disease: Why Lowering Your Cholesterol Won't Prevent Heart Disease-and the Statin-Free Plan that Will
by Jonny Bowden (Author), Stephen Sinatra (Author), Deirdre Rawlings (Author)


In The Great Cholesterol Myth Now Includes 100 Recipes for Preventing and Reversing Heart Disease, nutrition and health experts lay out detailed plans and recipes to help you prevent and reverse heart disease.

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 fat- Triglyceride to...

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: Cure for beginners - (NEW EDITION - UPDATED & EXPANDED) Understanding, Treating and Preventing High-Cholesterol (Cholesterol Cure Books - Cholesterol Treatment Book 1)

Cholesterol: Cure for beginners - (NEW EDITION - UPDATED & EXPANDED) Understanding, Treating and Preventing High-Cholesterol (Cholesterol Cure Books - Cholesterol Treatment Book 1)



Alarmed by your cholesterol rate? Or simply curious and health-conscious? This short guide will teach you the basics about cholesterol, its causes, symptoms and possible treatments.

2nd EDITION - UPDATED & EXPANDED

Today only, get this Amazon bestseller for just $2.99. Regularly priced at $4.99. Read on your PC, Mac, smart phone, tablet or Kindle device.

Cholesterol. It sounds like such a dirty word, but in the right amounts, cholesterol helps your body function. Unfortunately, your genes and your diet may leave you with way more than your system can handle. When there is too much cholesterol in your blood, it builds up in your arteries and can eventually cut off the blood supply to your heart. The higher your cholesterol, the greater your...

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...

The New 8-Week Cholesterol Cure

The New 8-Week Cholesterol Cure
by Robert E. Kowalski (Author)


Robert Kowalski's personal story is legendary. By the age of forty-one, he had suffered a heart attack and had undergone two coronary bypass surgeries. A traditional dietary approach to lowering his cholesterol failed dismally, and faced with the unpleasant alternative of a lifetime on medication, he created a program that proved astonishingly effective for him -- and legions of others worldwide who use it.Today Kowalski has beaten heart disease, lives an unlimited and vigorous lifestyle, and uses no prescription drugs. Now, with new information about risk factors, exercise, and supplements, The New 8-Week Cholesterol Cure is even more powerful in fighting heart disease.It includes:The facts about homocysteine and the deadly cholesterol Lp(a)A diet that jump starts cholesterol...

Cholesterol:The Great Cholesterol Hoax: Why Cholesterol Lowering Drugs Won't Help You Live One Day Longer And Drug Companies Know It (Cholesterol diet, ... Cholesterol lowering foods,heart disease)

Cholesterol:The Great Cholesterol Hoax: Why Cholesterol Lowering Drugs Won't Help You Live One Day Longer And Drug Companies Know It (Cholesterol diet, ... Cholesterol lowering foods,heart disease)


The Great Cholesterol Hoax: Why Cholesterol Lowering Drugs Won't Help You Live One Day Longer And Drug Companies Know It
Today only, get this amazingly informative and very popular book on cholesterol for just $3.33 Regularly priced at $6.99. Read on your PC, Mac, smart phone, tablet or Kindle device.

What if everything you've been told about cholesterol was lie, invented to benefit the drug makers?
You are about to discover the real truth behind America’s number #1 killer today that outweighs all cancers combined as the country’s biggest mass murderer to date. Over 600,000 people a year are killed by heart attacks.

Cholesterol medicine (statins) are now the world's most-prescribed form of medications. It is estimated that one in four Americans...

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)


From an award-winning cardiologist comes the most up-to-date, definitive reference book about statins—cholesterol-lowering drugs—providing a thorough examination of the uses and safety claims of this high-profile class of drugs.

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...

Low Cholesterol Meals: Grain Free Meals and Clean Eating for Low Cholesterol

Low Cholesterol Meals: Grain Free Meals and Clean Eating for Low Cholesterol
by Speedy Publishing Books


Low Cholesterol Meals: Grain Free Meals and Clean Eating for Low Cholesterol The Low Cholesterol Meals book covers two diet plans the clean eating diet and the grain free diet. Each of these diets works very well to bring cholesterol levels down to normal, lowering the bad cholesterol while raising the good cholesterol. High cholesterol puts a person at risk for having clogged arteries, which can cause high blood pressure, cardio vascular disorders, and strokes. These things are treatable by lowering the cholesterol levels through diet. When high cholesterol is diagnosed, the first line of action prescribed by most physicians is to diet and exercise. The first section covers the clean eating diet with these categories: The Clean Diet, Benefits of Clean Eating, Alternative Food Types, Tips...

© 2016 BrightSurf.com