Posts Tagged ‘Cholesterol’

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.

HERBAL TEA - BENEFITS AND LORE

Tuesday, March 1st, 2011

Boston, MA

These days, there is a lot of talk about health benefits from drinking teas. Green, black, and oolong are considered the three major classes, and each comes from the age old Camellia sinensis tea bush. But there is an even wider variety of herbal teas - infusions derived from anything other than C. sinensis.

Diane McKay and Oliver Chen
Antioxidants Research
Laboratory scientists
Diane McKay and Oliver Chen
Photo: Stephen Ausmus

According to folklore, some herbal teas also provide benefits. But there is little clinical evidence on the effects of drinking these teas. Now, Diane McKay and Jeffrey Blumberg have looked into science based evidence of health benefits from drinking three of the most popular herbals in America. McKay and Blumberg are with the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston, Massachusetts. Both work at the center’s Antioxidants Research Laboratory, which Blumberg directs.

One popular herbal, chamomile tea, has long been considered a soothing brew. In the early 20th century, it was mentioned in a classic children’s book about a little rabbit named Peter. At the end of a rough day, Peter’s mom served him some chamomile tea. Interestingly, when Blumberg and McKay reviewed scientific literature on the bioactivity of chamomile, they found no human clinical trials that examined this calming effect.

They did, however, publish a review article on findings far beyond sedation - describing test tube evidence that chamomile tea has moderate antioxidant and antimicrobial activities and significant antiplatelet clumping activity. Also, animal feeding studies have shown potent anti inflammatory action and some cholesterol lowering activity.

The researchers also published a review article describing evidence of bioactivity of peppermint tea. In test tubes, peppermint has been found to have significant antimicrobial and antiviral activities, strong antioxidant and antitumor actions, and some antiallergenic potential. When animals were fed either moderate amounts of ground leaves or leaf extracts, researchers also noted a relaxation effect on gastrointestinal tissue and an analgesic and anesthetic effect in the nervous system.

The researchers found several human studies involving peppermint oil, but they found no data from human clinical trials involving peppermint tea. McKay and Blumberg have concluded that the available research on herbal teas is compelling enough to suggest clinical studies.

McKay has led a human clinical trial to test whether drinking hibiscus tea affects blood pressure. She tested 65 volunteers, aged 30 to 70 years, who were pre or mildly hypertensive. Blood pressure readings of 120/80 or greater are considered a risk factor for heart disease, stroke, and kidney disease.

For 6 weeks, about half the group was randomly selected to drink 3 cups of hibiscus tea daily. The others drank a placebo beverage containing artificial hibiscus flavoring and color. All participants were advised to follow their usual diet and maintain their normal level of activity. Before the start of the study, blood pressure was measured twice - 1 week apart - and at weekly intervals thereafter.

The findings show that the volunteers who drank hibiscus tea had a 7.2 point drop in their systolic blood pressure (the top number), and those who drank the placebo beverage had a 1.3 point drop.

In a subgroup analysis of the 30 volunteers who had the highest systolic blood pressure readings (129 or above) overall at the start of the study, those assigned to drink hibiscus tea showed the greatest response to hibiscus tea drinking. Their systolic blood pressure went down by 13.2 points, diastolic blood pressure went down by 6.4 points, and mean arterial pressure went down by 8.7 points.

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The 2010 study was published in the Journal of Nutrition. “This data supports the idea that drinking hibiscus tea in an amount readily incorporated into the diet may play a role in controlling blood pressure, although more research is required,” says McKay.
By Rosalie Marion Bliss, Agricultural Research Service Information Staff.

This research is part of Human Nutrition, an ARS national program (#107) described at www.nps.ars.usda.gov.

Diane L. McKay is with the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111-1524; (781) 608-7183.

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

>>>>>Read more in our HeartVigor.com Herbal Tea Pages.

RESEARCHER LISTS MORE THAN 4,000 COMPONENTS OF BLOOD CHEMISTRY

Thursday, February 24th, 2011

Edmonton, Alberta - Feb. 24, 2011
After three years of exhaustive analysis led by a University of Alberta researcher, the list of known compounds in human blood has exploded from just a handful to more than 4,000. “Right now a medical doctor analyzing the blood of an ailing patient looks at something like 10 to 20 chemicals,” said U of A biochemist David Wishart. “We’ve identified 4,229 blood chemicals that doctors can potentially look at to diagnose and treat health problems.”

Hannah Gardener, Sc.D.
Dr. David Wishart
University of Alberta
biochemist
Photo: ualberta.ca

Blood chemicals, or metabolites, are routinely analyzed by doctors to diagnose conditions like diabetes and kidney failure. Wishart says the new research opens up the possibility of diagnosing hundreds of other diseases that are characterized by an imbalance in blood chemistry.

Wishart led more than 20 researchers at six different institutions using modern technology to validate past research, and the team also conducted its own lab experiments to break new ground on the content of human blood chemistry.

“This is the most complete chemical characterization of blood ever done,” said Wishart. “We now know the normal values of all the detectable chemicals in blood. Doctors can use these measurements as a reference point for monitoring a patient’s current and even future health.”

Wishart says blood chemicals are the “canary in the coal mine,” for catching the first signs of an oncoming medical problem. “The blood chemistry is the first thing to change when a person is developing a dangerous condition like high cholesterol.”

The database created by Wishart and his team is open access, meaning anyone can log on and find the expanded list of blood chemicals. Wishart says doctors can now tap into the collected wisdom of hundreds of blood research projects done in the past by researchers all over the world. “With this new database doctors can now link a specific abnormality in hundreds of different blood chemicals with a patient’s specific medical problem,” said Wishart.

Wishart believes the adoption of his research will happen slowly, with hospitals incorporating new search protocols and equipment for a few hundred of the more than 4,000 blood-chemistry markers identified by Wishart and his colleagues.

“People have being studying blood for more than 100 years,” said Wishart. “By combining research from the past with our new findings we have moved the science of blood chemistry from a keyhole view of the world to a giant picture window.”

>>>>>Read all the latest 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

SCIENTISTS SOLVE MYSTERY OF POLYKETIDE DRUG FORMATION

Wednesday, May 21st, 2008

Discovery of enzyme role could lead to development of new drugsMany top-selling drugs used to treat cancer and lower cholesterol are made from organic compounds called polyketides, which are found in nature but historically difficult for chemists to alter and reproduce in large quantities.
For the first time, scientists at UC Irvine have discovered how polyketides form their ringlike shape, making it easier for chemists to manipulate them into new drugs.
 Polyketide (Tetracycline) The key, they found, is an enzyme called aromatase/cyclase, which forms a C-shape mold in which polyketides can form one molecule at a time. By changing this mold, chemists can control the size and shape of the polyketide, resulting in the formation of new drugs.
“Almost every polyketide has rings in its chemical structure, and if we can control ring formation, we can produce more polyketide drugs,” said Sheryl Tsai, lead author of this study and an assistant professor of molecular biology and biochemistry and chemistry at UCI. “Until now, polyketide ring formation was a mystery that hampered our efforts to produce new drugs.”
The research appears online this week in the Proceedings of the National Academy of Sciences.
Polyketide-based drugs and products account for more than $35 billion in sales annually. They include antibiotics that can cure a bacteria infection (tetracycline and erythromycin); anti-cancer drugs used in chemotherapy (doxorubicin and mithramycin); anti-oxidants that help prevent cancer and promote heart strength (EGCG and resverastrol); and drugs that lower cholesterol levels (Zocor). Green tea and red wine also contain beneficial polyketides.
Polyketides are made naturally by bacteria, fungi, plants and marine animals. Those organisms produce polyketides to kill their predators, be it another bacteria or fungi. They can produce different types of polyketides that kill different types of enemies.
“Because bacteria do not have arthritis or diabetes, they would not evolutionally select polyketides that could be used for arthritis or diabetes treatment,” Tsai said. “But we can coax the bacteria to do precisely that, if we can control the ring formation in the polyketides.”
Prior to this study, it was not known how nature controls the polyketide ring shape, which is essential for antibiotic and anti-cancer properties.
By using molecular cloning and chemical biology techniques, Tsai and her scientific team discovered that the aromatase/cyclase enzyme has a pocket that shapes the polyketide, promoting a unique ring pattern.
Said Tsai: “We hope this will lead to the development of new drugs in such areas as cancer therapeutics, obesity treatment and stem cell research.”
UCI scientists Brian Ames, Tyler Korman, Peter Smith, Thanh Vu, along with UCLA researchers Yi Tang and Wenjun Zhang, also worked on this study, which was funded by the Pew Foundation and the National Institutes of Health.Source: University of California, Irvine/News Release

AGGRESSIVE LIPID-LOWERING BENEFITS BYPASS PATIENTS

Tuesday, May 20th, 2008

In patients who have had heart bypass surgery, taking the cholesterol-lowering drug Lipitor at a dose of 80 milligrams per day, rather than 10 milligrams per day, can markedly improve outcomes, new research shows.

Major heart-related “events” fell by 27 percent and the need for repeat heart procedures dropped by 30 percent with use of higher-dose Lipitor, researchers found.

Because heart bypass surgery patients represent an “especially high-risk population that tends to be under treated with lipid-lowering therapy, this treatment should be the new standard of care,” with the goal of reducing heart-related illness and death, they conclude.

The findings stem from a post-hoc analysis of the Treating to New Targets, or TNT, trial.

As part of the trial, 4,654 patients who had heart bypass surgery were randomized to receive Lipitor (also called atorvastatin) at the lower or higher dose and were followed for a median of 4.9 years.

By the end of the study, the average levels of “bad” LDL-cholesterol were much lower in patients taking 80 milligrams of Lipitor daily than in those taking 10 milligrams daily, Dr. Sanjiv J. Shah, from San Francisco General Hospital, and colleagues report.

Moreover, 9.7 percent of those taking high-dose Lipitor suffered a major cardiovascular event (cardiac death, nonfatal heart attack, resuscitated cardiac arrest, or stroke) compared with 13 percent of patients taking low-dose Lipitor.

There were also fewer repeat bypass operations or angioplasty procedures in the higher dose arm of the study (11.3 percent vs. 15.9 percent).

This study, conclude Shah and colleagues, shows that “aggressive lipid-lowering” with atorvastatin 80 mg decreases major cardiovascular events and the need for repeat heart procedures in patients who’ve had heart bypass surgery.
SOURCE: Journal of the American College of Cardiology, May 20, 2008.