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


Poor response to cholesterol drugs may indicate blocked arteries
If your "bad" cholesterol level stays the same or increases after you take statin drugs, you may have more blocked arteries than people whose levels drop, according to research in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology.

Synthetic biology breakthrough leads to cheaper statin production
University of Manchester researchers, together with industrial partner DSM, have developed a single-step fermentative method for the production of leading cholesterol-lowering drug, pravastatin, which will facilitate industrial-scale statin drug production.

Women veterans younger, more depressed when referred for heart test
Women veterans who had specialized heart tests were younger and more likely to be obese, depressed and suffer from post-traumatic stress disorder than men veterans, according to a study published in an American Heart Association journal.

Feast-and-famine diet could extend life, study shows
Think of it as interval training for the dinner table. University of Florida Health researchers have found that putting people on a feast-or-famine diet may mimic some of the benefits of fasting, and that adding antioxidant supplements may counteract those benefits.

Million man study examines long-term effects of blocking inflammation
Inflammation - the body's response to damaging stimuli - may have a protective effect against cardiovascular disease, according to a study published today in the journal Lancet Diabetes and Endocrinology.

Singapore scientists discover unique risk variants of age-related macular degeneration in East Asians
Age-related macular degeneration (AMD) is a major cause of blindness in the elderly in Singapore and worldwide. By 2040, global projected cases of AMD are 288 million, with the largest number of cases in Asia (113 million).

Patients with mental illness less likely to receive diet, exercise advice
More than half of patients with symptoms of mental illness - and nearly one-third of those who also had diabetes - said their health care providers had never told them to exercise or reduce their intake of dietary fat, according to a new study published in Diabetes Educator.

Keep calm, anger can trigger a heart attack!
University of Sydney research reveals that the risk of a heart attack is 8.5 times higher in the two hours following a burst of intense anger.

Asphaltene analysis takes a giant step
Rice University researchers have developed an easy and accurate technique to detect and quantify the amount of asphaltene precipitated from crude oils, which bedevils the oil industry by clogging wells and flow lines.

Safety and life-saving efficacy of statins have been exaggerated, says USF scientist
Hailed as miracle drugs when they hit the market two decades ago, statins, the cholesterol-lowering drugs prescribed to prevent heart attacks, are not as effective nor as safe as we have been led to believe.
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:The Great Cholesterol Hoax: Why Cholesterol Lowering Drugs Won't Help You Live One Day Longer And Drug Companies Know It (Cholesterol diet,Cholesterol ... 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 ... 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 $3.23. Regularly priced at $4.99. 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...

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...

Cholesterol Diet: The Ultimate Solution to Lower Your Cholesterol Without Drug (Weight Loss Motivation Strategies, Cholesterol Solution, Lower Cholesterol Naturally, Heart Disease Prevention)

Cholesterol Diet: The Ultimate Solution to Lower Your Cholesterol Without Drug (Weight Loss Motivation Strategies, Cholesterol Solution, Lower Cholesterol Naturally, Heart Disease Prevention)
by Weight Loss Motivation - Healthy Weight Loss Diet


The Ultimate Solution to Lower Your Cholesterol Without Drug
Cholesterol is an important substance that your body need. There are 3 types of cholesterol – the bad cholesterol (LDL), good cholesterol (HDL) and triglycerides. If your bad cholesterol level is higher than the normal level in your bloodstream, it causes blockage of your arteries. However, there are things that you can do to manage cholesterol levels and lower your risk.

High cholesterol is one of the health problems that are affecting millions of people all over the world. It is considered as one of the major risk factors for heart disease. You will have difficulties in dealing with it if you are not aware what cholesterol is. There are lots of myths and misconceptions about cholesterol, which worsen...

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 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 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...

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,...

The Cholesterol Cure: Understanding, Treating and Preventing High-Cholesterol

The Cholesterol Cure: Understanding, Treating and Preventing High-Cholesterol


The Cholesterol Cure:Understanding, Treating and Preventing High-Cholesterol

Today only, get this Amazon bestseller for just $0.99. 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 chances are of developing heart disease.

There are several types of cholesterol in your body, but the ones in the spotlight at the...

The Cholesterol Solution: The Top 10 Ways to Naturally Lower Your Cholesterol & Live a Healthier Life

The Cholesterol Solution: The Top 10 Ways to Naturally Lower Your Cholesterol & Live a Healthier Life


Don't Let High Cholesterol Shorten Your Life! Learn to Lower Cholesterol and Live Healthy the Natural Way.

***Get this Amazon Best Seller now for the special promotion price of $2.99! Regularly priced at $4.99***

Having high cholesterol is widely known to be a troublesome condition that can lead to heart attacks, strokes, and other serious and life-threatening health problems. Unfortunately, you may not know you have high cholesterol until it's nearly too late! This book will tell you important information such as what kind of people are at a higher risk of getting high cholesterol, what roles cholesterol plays in your body, and, most importantly, how to lower it safely and naturally. If you or someone you know has high cholesterol, the ten natural methods to...

© 2015 BrightSurf.com