Posts Tagged ‘LDL’

NEW ADVANCE ANNOUNCED IN REDUCING ‘BAD’ CHOLESTEROL

Thursday, December 8th, 2011

Leicester, UK

Researchers identify enzyme that could be targeted to help body tackle LDL’s

Scientists from the University of Leicester and the University of California Los Angeles (UCLA) have announced a major advance towards developing drugs to tackle dangerous, or ‘bad’, cholesterol in the body.

Prof. John Schwabe
Prof. John Schwabe
University of Leicester
Prof. of Structural Biology
Photo:le.ac.uk

They have filed two patents for developing targeted drugs that would act as a catalyst for lowering levels of ‘bad’ cholesterol. Two research papers published by the academics enhance the understanding of the regulation of low density lipoprotein (LDL) or “bad” cholesterol.

LDL, the so called ‘bad’ cholesterol, is often linked to medical problems like heart disease, stroke and clogged arteries.

In the body, cells in the liver produce an LDL receptor that binds LDL and removes it from the blood, thereby lowering cholesterol levels.

The scientists have characterised an enzyme called IDOL that plays a key role in regulating the amount of LDL receptor available to bind with ‘bad’ cholesterol. Therefore targeting the enzyme with drugs could increase the levels of LDL receptors present, thus lowering circulating cholesterol in humans.

Professor John Schwabe, Head of Biochemistry at the University of Leicester, said: “Development of a drug that interferes with IDOL’s activity could help lower levels of LDL. Our research has greatly enhanced our understanding of this important process.”

Prof John Schwabe, Dr Ben Goult and Dr Louise Fairall at the University of Leicester in collaboration with the University of California Los Angeles (UCLA) published their research in the top research journals: Genes & Development and the Proceedings of the National Academy of Science (PNAS). The research was funded by The Wellcome Trust, the NIH and the Howard Hughes Medical Institute.

The study published in Genes & Development announced the first atomic structural information on IDOL and identified the E2 ligase, UBE2D that works with IDOL to degrade the LDL receptor.

In the second research article published in PNAS, the team elucidated the molecular basis for the stringent specificity of IDOL for the LDL receptor.

Professor Schwabe added: “Remarkably, IDOL only targets three proteins for degradation (all lipoprotein receptors) and this research paper greatly enhances our understanding of this specificity and identifies key residues involved in mediating this interaction.”

“A potential future drug that targets IDOL could be prescribed in conjunction with statin drugs, which also cut cholesterol levels by increasing production of the LDL receptor and these two studies make considerable headway towards this.”

>>>>>Read all the latest in our HeartVigor.com News Page.

NEW EXPLANATION FOR HEART HEALTHY BENEFITS OF CHOCOLATE

Monday, February 7th, 2011

WASHINGTON

In time for the chocolate giving and chocolate noshing fest on Valentine’s Day, scientists are reporting discovery of how this treat boosts the body’s production of high density lipoprotein cholesterol (HDL) - the “good” form of cholesterol that protects against heart disease. Just as those boxes of chocolates get hearts throbbing and mouths watering, polyphenols in chocolate rev up the activity of certain proteins, including proteins that attach to the genetic material DNA in ways that boost HDL levels. Their report appears in the Journal of Agricultural and Food Chemistry, one of 39 peer-reviewed scientific journals published by the American Chemical Society.

Midori Natsume, Ph.D., and colleagues note that studies have shown that cocoa, the main ingredient in chocolate, appears to reduce the risk of heart disease by boosting levels of HDL, or “good” cholesterol, and decreasing levels of low-density lipoprotein (LDL), or “bad” cholesterol. Credit for those heart-healthy effects goes to a cadre of antioxidant compounds in cocoa called polyphenols, which are particularly abundant in dark chocolate. Until now, however, nobody knew exactly how the polyphenols in cocoa orchestrated those beneficial effects.

The scientists analyzed the effects of cocoa polyphenols on cholesterol using cultures of human liver and intestinal cells. They focused on the production of apolipoprotein A1 (ApoA1), a protein that is the major component of “good” cholesterol, and apolipoprotein B (ApoB), the main component of “bad” cholesterol. It turns out that cocoa polyphenols increased ApoA1 levels and decreased ApoB levels in both the liver and intestine. Further, the scientists discovered that the polyphenols seem to work by enhancing the activity of so-called sterol regulatory element binding proteins (SREBPs). SREBPs attach to the genetic material DNA and activate genes that boost ApoA1 levels, increasing “good” cholesterol. The scientists also found that polyphenols appear to increase the activity of LDL receptors, proteins that help lower “bad” cholesterol levels.

Other recent research on the health benefits chocolate published in ACS journals:

* New evidence that dark chocolate helps ease emotional stress

* Study finds that people are programmed to love chocolate

* Natural ACE inhibitors in chocolate, wine and tea may help lower blood pressure

>>>>>Read all the latest in our HeartVigor.com News Page.

CHOLESTEROL’S LINK TO HEART DISEASE GETS CLEARER

Tuesday, February 2nd, 2010

Cholesterol’s link to heart disease gets clearer - and more complicated
By considering molecular level events on a broader scale, researchers now have a clearer, if more complicated, picture of how one class of immune cells goes wrong when loaded with cholesterol. The findings reported in the February 3rd issue of Cell Metabolism, a Cell Press publication, show that, when it comes to the development of atherosclerosis and heart disease, it’s not about any one bad actor - it’s about a network gone awry.

The new findings also highlight a pretty remarkable thing, Heinecke says: “Despite 30 years of study, we still don’t know how cholesterol causes heart disease.” But, with the new findings, scientists are getting closer.

Earlier studies had shown that heart disease is about more than just high LDL (”bad”) cholesterol. Cells known as macrophages also play a critical role. Macrophages are part of the innate immune system that typically gobble up pathogens and clear away dead cells. But they also take up and degrade cholesterol derivatives. When they get overloaded with those lipoproteins, they take on a foamy appearance under the microscope to become what scientists aptly refer to as foam cells. Those foam cells are the ones that seem to have critical importance in the development of atherosclerosis.

People had typically thought about this problem in terms of linear pathways, Heinecke explained. In essence, macrophages end up with too much cholesterol going in and not enough coming out. The macrophages get overwhelmed and trapped in the artery wall, and somehow plaques form as a result.

But the new results show that it isn’t really about simple paths in and out; rather, there is an integrated network of macrophage proteins involved. When that network gets disrupted, as it does when too much cholesterol comes in, atherosclerosis forms. “It’s definitely a different way to think about what is going on,” Heinecke says.

Heinecke’s group applied sophisticated technologies and statistical tools to get a global view of what happens to macrophage proteins when they turn into foam cells. Their analysis revealed what they call a macrophage sterol responsive network (MSRN), including proteins already known to work together. Most of them are also found in one place, within microvesicles outside the macrophage cells.

>>>>>Read the full Press Release in our HeartVigor.com News Pages.

5 TIPS TO INCREASE HDL CHOLESTEROL

Thursday, May 29th, 2008

Thanks to powerful cholesterol-lowering statin drugs, driving down low-density lipoprotein (LDL), or “bad” cholesterol, has been the primary approach to improving cholesterol levels. But there’s more to the story of cholesterol and cardiovascular risk than LDL alone. Another key player is high-density lipoprotein (HDL), the “good” cholesterol. Higher levels of HDL are associated with lower cardiovascular risk. The good news about this good cholesterol is that simple lifestyle changes can help boost HDL, reports the June 2008 issue of Harvard Women’s Health Watch.

HDL removes LDL from artery walls and ferries it to the liver for processing or removal. HDL also fights potentially dangerous inflammation and clot formation. According to a recent review of research on HDL, there’s some evidence that increasing HDL can reduce the risk of heart attack and stroke even without changes in LDL.

Harvard Women’s Health Watch suggests several things people can do to nudge up HDL levels. Most of these strategies also improve health in other ways.

1. Get aerobic exercise. Moderate to vigorous aerobic exercise can boost HDL by 5% to 10%. Aim for five 30-minute sessions per week.

2. Lose weight if you need to. If you’re overweight or obese, you can boost your HDL level by about 1 mg/dL for every seven pounds lost, although any amount of weight loss will help.

3. If you smoke, quit. HDL levels rise by as much as 15% to 20% after you quit.

4. Eat a healthy diet. Avoid trans fats, which increase bad cholesterol and decrease good cholesterol. Avoid highly refined carbohydrates, such as white-flour products.

5. Consider medications. Niacin, available over the counter, is the most effective HDL-raising medication available. Niacin can be strong medicine work with your clinician if you want to try it.

Source: www.health.harvard.edu