(Yale University)
A new method of growing arteries could lead to a “biological bypass”-or a non-invasive way to treat coronary artery disease, Yale School of Medicine researchers report with their colleagues in the April issue of Journal of Clinical Investigation.

Michael Simons,MD - chief of the Section of Cardiology at Yale School of Medicine photo: yalemedicalgroup.org

Coronary arteries can become blocked with plaque, leading to a decrease in the supply of blood and oxygen to the heart. Over time this blockage can lead to debilitating chest pain or heart attack. Severe blockages in multiple major vessels may require coronary artery bypass graft surgery, a major invasive surgery.

“Successfully growing new arteries could provide a biological option for patients facing bypass surgery,” said lead author of the study Michael Simons, M.D., chief of the Section of Cardiology at Yale School of Medicine.

In the past, researchers used growth factors-proteins that stimulate the growth of cells-to grow new arteries, but this method was unsuccessful. Simons and his team studied mice and zebrafish to see if they could simulate arterial formation by switching on and off two signaling pathways-ERK1/2 and P13K.

“We found that there is a cross-talk between the two signaling pathways. One half of the signaling pathway inhibits the other. When we inhibit this mechanism, we are able to grow arteries,” said Simons. “Instead of using growth factors, we stopped the inhibitor mechanism by using a drug that targets a particular enzyme called P13-kinase inhibitor.”

“Because we’ve located this inhibitory pathway, it opens the possibility of developing a new class of medication to grow new arteries,” Simons added. “The next step is to test this finding in a human clinical trial.”

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An Agricultural Research Service (ARS) scientist is helping to sort through the jumbled genetics of Echinacea, the coneflower known for its blossoms - and its potential for treating infections, inflammation, and other human ailments.

An ARS scientist is studying the jumbled genetics of Echinacea, the coneflower known for its blossoms-and its potential for treating infections, inflammation, and other human ailments. photo: David Cappaert, MSU

Only a few Echinacea species are currently cultivated as botanical remedies, and plant breeders would like to know whether other types also possess commercially useful traits. ARS horticulturist Mark Widrlechner, who works at the ARS North Central Regional Plant Introduction Station (NCRPIS) in Ames, Iowa, is partnering in research to find out how many distinct Echinacea species exist. Previous studies have put the number between four and nine species, depending on classification criteria.

Working with Iowa State University scientists, Widrlechner selected 40 diverse Echinacea populations for DNA analysis from the many populations conserved at the NCRPIS. Most of these Echinacea populations were found to have a remarkable range of genetic diversity.

DNA analysis suggested that when much of North America was covered with glaciers, Echinacea found southern refuges on both sides of the Mississippi River. But when the glaciers receded after thousands of years, the groups came together as they moved northward and began to hybridize, which might have blurred previous genetic distinctions.

The research team also analyzed the same populations for chemical differences in root metabolites. These metabolites, which are often essential for survival and propagation, can vary widely among species and may have benefits for human health.

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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.

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New research findings from a team at the Providence Heart + Lung Institute at St. Paul’s Hospital and the University of British Columbia (UBC) may lead to new treatment options for abdominal aortic aneurysms (AAA) - a potentially fatal disease that currently has no pharmacological treatments.

“Dr. David Granville University of British Columbia and St. Paul’s Hospital photo: UBC

An aortic aneurysm is a bulging of the aorta, the largest blood vessel in the body. If the aneurysm ruptures, it causes rapid blood loss and a high risk of death. About 75 per cent of all aortic aneurysms occur in the part of the aorta that is located in the abdomen, which supplies blood to the lower limbs.

Published in today’s American Journal of Pathology, a study led by Dr. David Granville, a researcher with UBC and the Providence Heart + Lung Institute, reveals a novel therapeutic target for AAA that could have a major impact on the treatment of this disease.

Using experimental models of AAA, Dr. Granville and his team identified a protein degrading enzyme called Granzyme B that is abundant in aneurysms. To determine whether Granzyme B was contributing to aneurysms, the enzyme was genetically knocked out.

“When we removed Granzyme B, we found that it not only slowed the progression of aneurysms, but also markedly improved survival,” says Dr. Granville. “This suggests that drugs designed specifically to target Granzyme B could be an effective means of treating aneurysms.”

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Universite de Montreal research team developing leptin based pill to control hunger. A Universite de Montreal research team is developing a pill composed of leptin, the protein that tells our brain to stop eating. “Mice deprived of leptin will not stop eating. They become so big they have trouble moving around,” says Moise Bendayan, a pathology professor at the Universite de Montreal Faculty of Medicine who has studied the leptin protein extensively.

“Dr Moise Bendayan Universite de Montreal Faculty of Medicine photo: Universite de Montreal

Leptin regulates appetite in mammals and its levels decrease when fasting and rise during meals. It has been proven to be an appetite suppressant when administered intravenously to pathologically obese people.

Postdoctoral student Philippe Cammisotto is leading the charge for a leptin based, appetite suppressing pill with Dr. Bendayan and Emile Levy, a professor from the Department of Nutrition. “Taken orally, such a pill would provide obese people with the sensation of being full. They would eat less and in turn lose weight,” says Dr. Cammisotto.

“We hope to start animal testing in 2010,” says Bendayan. “The molecule is easy to synthesize and the protocol is ready.”

After decades of building his reputation in fundamental research, Bendayan is happy to collaborate on something more tangible. “Obesity is a big problem in our society, no pun intended,” says Bendayan. “To develop medication to combat obesity would be a great way for our laboratory to contribute to public health.”

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Protein completely restores motor function; scientists hope it will help humans.
People with impaired mobility after a stroke soon may have a therapy that restores limb function long after the injury, if a supplemental protein works as well in humans as it does in paralyzed rats. Two new studies by UC Irvine biologists have found that a protein naturally occurring in humans restores motor function in rats after a stroke. Administered directly to the brain, the protein restores 99 percent of lost movement; if it’s given through the nose, 70 percent of lost movement is regained. Untreated rats improve by only 30 percent.

James Fallon mobilizes existing stem cells, causing them to proliferate, migrate and eventually differentiate into new cells (shown by the red area back left) that fill in the damaged brain, returning function to to the stroke victim. photo: Daniel A. Anderson

“No drugs exist that will help a stroke after a few days. If you have a stroke, you don’t have many treatment options,” said James Fallon, psychiatry & human behavior professor and senior coauthor of the studies. “Now we have evidence there may be therapies that can repair damage to a significant degree long after the stroke. It’s a completely unexpected and remarkable finding, and it’s worth trying in humans.”

The studies, carried out by UCI postdoctoral researcher Magda Guerra-Crespo, chronicle the success of a small protein called transforming growth factor alpha, which plays critical tissue forming and developmental roles in humans from just after conception through birth and into old age.

“TGF alpha has been studied for two decades in other organ systems but never before has been shown to reverse the symptoms of a stroke,” Guerra-Crespo said. No lasting side effects were observed.

In the first study, published in the journal Neuroscience, scientists sought to learn whether TGF alpha administered directly to the brain could help rats with stroke-induced loss of limb function, typically on one side - as is seen in humans.

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Regulate trans fats now.
The Heart and Stroke Foundation calls on the federal government to live up to the commitment made two years ago to regulate trans fats in Canada’s food supply, based on Health Canada’s final set of monitoring results released today. “Canada’s trans fat verdict is in,” says Sally Brown, CEO of the Heart and Stroke Foundation of Canada. “This fourth and final round of monitoring has demonstrated that levels of heart clogging trans fats are still far too prevalent in our food.

They can even be found at dangerous levels in foods in children’s hospitals - the very places that are meant to improve the health of our children. Without government intervention, the trend will sadly continue.”

This final set of data focused on small and medium sized restaurants and fast food chains, as well as other institutions such as high schools, CEGEPs, movie theatres, hospitals and universities.

“Once again, the levels of trans fats in baked goods, pastries and cookies, products which are frequently consumed by children, is particularly disturbing,” says Brown.

Fourth round data shows 21 per cent of French fries, 26 per cent of chicken products, 50 per cent of bakery products and 60 per cent of cookies are still made with high levels of trans fats. “Without a clear signal to the market, oil producers will not produce healthy alternatives that can be used in majority of food categories that have remained an issue.”

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Famous for its antioxidant properties and role in tissue repair, vitamin C is touted as beneficial for illnesses ranging from the common cold to cancer and perhaps even for slowing the aging process. Now, a study published online on December 24th by Cell Press in the journal Cell Stem Cell uncovers an unexpected new role for this natural compound: facilitating the generation of embryonic like stem cells from adult cells. Over the past few years, we have learned that adult cells can be reprogrammed into cells with characteristics similar to embryonic stem cells by turning on a select set of genes. Although the reprogrammed cells, called induced pluripotent stem cells (iPSCs), have tremendous potential for regenerative medicine, the conversion is extremely inefficient.

“The low efficiency of the reprogramming process has hampered progress with this technology and is indicative of how little we understand it. Further, this process is most challenging in human cells, raising a significant barrier for producing iPSCs and serious concerns about the quality of the cells that are generated,” explains senior study author Dr. Duanqing Pei from the South China Institute for Stem Cell Biology and Regenerative Medicine at the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences.

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Scientists in Sweden are reporting for the first time that a group of drugs used to treat heart failure shows promise for fighting colon cancer. The study is in ACS’ Journal of Natural Products, a monthly publication. Colon cancer is the third most common cancer in the United States, with more than 150,000 cases diagnosed in the U.S. each year.

The leaves of the oriental foxglove plant contain digitoxin, a drug used to treat heart disease. It is in a family of medications that now show promise for fighting colon cancer photo: Wikimedia Commons

Jenny Felth, Joachim Gullbo, and colleagues note that cardiac glycosides are a family of naturally derived drugs used to treat congestive heart failure and abnormal heart rhythms. Scientists have suspected for some time, based on previous research, that these heart drugs may have promise for fighting many different types of cancer. Despite this, knowledge on effects in colon cancer or combination effects with other anti cancer drugs is lacking. But scientists know little about their potential anticancer effects and have not tested these substances against colon cancer.

As part of a larger study to screen and identify natural substances with activity against colon cancer, the scientists picked several cardiac glycosides for further study. They tested five of these heart drugs against laboratory cultures of human colon cancer cells and found that they were all effective, to varying degrees, at killing the cancer cells. The sensitivity, however, was rather low when compared to that of other cancer cell types reported previously. Several of the drugs also showed increased anticancer activity when combined with certain drugs used for standard chemotherapy. The findings suggest that these heart drugs may affect colon cancer outcome when used alone or in combination with conventional chemotherapy drugs, they say.

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If you’ve been waiting for the day to arrive when computers actually start performing surgery, that moment might soon be upon us. A French team has developed a computerized 3D model that allows surgeons to use robotics to operate on a beating heart, according to a report in The International Journal of Robotics Research, published by SAGE.

The robotic technology predicts the movement of the heart as it beats, enabling the surgical tools to move in concert with each beat. It means that the surgeon can perform a procedure as if the heart was stationary. This development could be very important for millions of patients who require less invasive surgical heart procedures, where stopping the heart from beating would cause unnecessary risk.

Rogerio Richa, Philippe Poignet and Chao Liu from France’s Montpellier Laboratory of Informatics, Robotics, and Microelectronics developed a three dimensional computerized model that tracks the motion of the heart’s surface as it beats. In addition to the heart, this model also accounts for the movement of a patient’s chest wall during breathing. Known as the “thin-plate spline deformable model”, this new computerized approach allows the robotic arm to continually adjust to heart and chest movements during surgery.

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HOUSTON - The second phase of a clinical trial testing a new stem cell based therapy on injured heart muscle has been launched by researchers at The University of Texas Medical School at Houston. It is the only study site in the Texas Medical Center.

Patient Melvin Dyess, far right, participates in phase II of a stem cell trial at the University of Texas Medical School at Houston, where Dr. Ali Denktas, center, is the lead investigator. photo: Deborah Mann Lake

Results from Phase I of the trial are published in today’s issue of the Journal of the American College of Cardiology. Researchers reported that patients were treated safely with intravenous adult human mesenchymal stem cells (Prochymal) after a heart attack. In addition, they had fewer arrhythmias, improved heart and lung function, and improvement in overall condition.

“We are able to use a stem cell product that is on the shelf without prior preparation of anything from the patient, and this product appears to be able to help the heart muscle recover after a heart attack,” said Ali E. Denktas, M.D., the trial’s Houston site principal investigator and assistant professor of cardiology at the UT Medical School at Houston. “This means patients have the potential to recover quicker with less risk of an immediate secondary attack.”

In many cell based therapies, doctors harvest the patient’s own cells, process them and then return them to the patient. Prochymal, developed by Osiris Therapeutics, Inc., contains adult mesenchymal stem cells from healthy donors. The cells can be stored at an emergency center until needed. For purposes of the Phase II study, Prochymal must be administered within seven days of a heart attack.

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(CHICAGO) - Adult stem cells may help repair heart tissue damaged by heart attack according to the findings of a new study to be published in the December 8 issue of the Journal of the American College of Cardiology. Results from the Phase I study show stem cells from donor bone marrow appear to help heart attack patients recover better by growing new blood vessels to bring more oxygen to the heart. Rush University Medical Center was the only Illinois site and one of 10 cardiac centers across the country that participated in the 53 patient, double-blind, placebo-controlled Phase I trial. Rush is now currently enrolling patients for the second phase of the study.

Researchers say it is the strongest evidence thus far indicating that adult stem cells can actually differentiate, or turn into heart cells to repair damage. Until now, it has been believed that only embryonic stem cells could differentiate into heart or other organ cells.

“The results point to a promising new treatment for heart attack patients that could reduce mortality and lessen the need for heart transplants,” said Dr. Gary Schaer, head of the Rush Cardiac Catheterization Laboratory and study principal investigator at Rush.

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Study suggests future way to identify vulnerable people

ANN ARBOR, Mich. - Previous studies have shown a link between low vitamin D status and heart disease. Now a new study shows that patients with high blood pressure who possess a gene variant that affects an enzyme critical to normal vitamin D activation are twice as likely as those without the variant to have congestive heart failure.

“This study is the first indication of a genetic link between vitamin D action and heart disease,” says Robert U. Simpson, professor of pharmacology at the University of Michigan Medical School and one of the authors of the study in the journal Pharmacogenomics.

“This study revealed that a critical enzyme absolutely required for production of the vitamin D hormone has a genetic variant associated with the development of congestive heart failure,” Simpson says. “If subsequent studies confirm this finding and demonstrate a mechanism, this means that in the future, we may be able to screen earlier for those most vulnerable and slow the progress of the disease.” Such a screening test would be years away.

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CORVALLIS, Ore. - A string of recent discoveries about the multiple health benefits of vitamin D has renewed interest in this multi purpose nutrient, increased awareness of the huge numbers of people who are deficient in it, spurred research and even led to an appreciation of it as “nature’s antibiotic.” On issues ranging from the health of your immune system to prevention of heart disease and even vulnerability to influenza, vitamin D is now seen as one of the most critical nutrients for overall health. But it’s also one of those most likely to be deficient - especially during winter when production of the “sunshine vitamin” almost grinds to a halt for millions of people in the United States, Europe and other northern temperate zones.

Analogs of the vitamin are even being considered for use as new therapies against tuberculosis, AIDS, and other concerns. And federal experts are considering an increase in the recommended daily intake of the vitamin as more evidence of its value emerges, especially for the elderly.

“About 70 percent of the population of the United States has insufficient levels of vitamin D,” said Adrian Gombart, a principal investigator with the Linus Pauling Institute at Oregon State University. “This is a critical issue as we learn more about the many roles it may play in fighting infection, balancing your immune response, helping to address autoimmune problems, and even preventing heart disease.”

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HOUSTON - Green tea extract has shown promise as cancer prevention agent for oral cancer in patients with a premalignant condition known as oral leukoplakia, according to researchers at The University of Texas M. D. Anderson Cancer Center. The study, published online in Cancer Prevention Research, is the first to examine green tea as a chemopreventative agent in this high risk patient population. The researchers found that more than half of the oral leukoplakia patients who took the extract had a clinical response.

Long investigated in laboratory, epidemiological and clinical settings for several cancer types, green tea is rich in polyphenols, which have been known to inhibit carcinogenesis in preclinical models. Still, clinical results have been mixed.

“While still very early, and not definitive proof that green tea is an effective preventive agent, these results certainly encourage more study for patients at highest risk for oral cancer,” said Vassiliki Papadimitrakopoulou, M.D., professor in M. D. Anderson’s Department of Thoracic/Head and Neck Medical Oncology, and the study’s senior author. “The extract’s lack of toxicity is attractive - in prevention trials, it’s very important to remember that these are otherwise healthy individuals and we need to ensure that agents studied produce no harm.”

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