Atlanta, Gorgia - August 13, 2010
Isolating cells from a patient’s blood or bone marrow that nourish blood vessels may be a safer and less arduous route to treatment of cardiovascular disease than obtaining rare stem cells, according to research from Emory University School of Medicine.

Young-sup Yoon, MD, Ph.D Emory University School of Medicine Photo: stemyoon.org

In recent clinical trials, doctors in several countries have tested the ability of a patient’s bone marrow cells to repair damage, such as heart attacks and peripheral artery disease, created by problems of blood flow.

“The focus has been on stem cells, but it looks like the main beneficial effects come from transplanted cells’ ability to support the growth of nearby blood vessels,” says senior author Young-sup Yoon, MD, PhD, associate professor of medicine (cardiology) at Emory University School of Medicine. “Based on this idea, we wanted to identify a population of cells enriched with the capacity to regenerate blood vessels.”

The blood vessel repairing properties of selected cells from human blood were described in the Aug. 10 issue of the Journal of the American College of Cardiology, with a related paper on cells derived from mouse bone marrow published online July 15 by the journal Circulation Research.

The first author of the JACC paper is postdoctoral fellow Sung-Whan Kim, PhD. The first author of the Circulation Research paper is Hyongbum Kim, MD, PhD, now an assistant professor in Korea.

Yoon’s team focused on the molecule CD31, also known as platelet endothelial cell adhesion molecule-1 or PECAM-1, because of its presence on endothelial cells - the cells that form the inner lining of blood vessels. In experiments with donated blood from human volunteers or mouse bone marrow cells, the researchers showed that cells with CD31 on their surfaces secrete hormones that support the growth of blood vessels.

About a third of the cells in the blood or bone marrow have CD31 on their surfaces, including some differentiated immune cells. In culture, sorted cells displaying CD31 can form tubular structures mimicking the growth of blood vessels in the body.

“We can show that after transplantation, some CD31 positive cells do become endothelial cells, but their main effect is more to support other cells than to become the building blocks,” Yoon says.

The researchers used antibodies against CD31 to sort human blood or mouse bone marrow cells into two groups: cells with CD31 and those without. They then tested these cells’ ability to spur blood vessel regrowth in mice whose hind legs had a blocked blood supply.

In the project described in Circulation Research, after two weeks more than 80 percent of the mouse hind legs transplanted with CD31 positive bone marrow cells survived, while less than 15 percent of the legs transplanted with CD31 negative cells survived. In laser Doppler images, the mice with CD31 positive cells injected into their legs had greatly enhanced blood flow and an increased number of capillaries.

Yoon says harvesting CD31 positive cells may have several advantages compared to previous methods of treating cardiovascular disease. The cells can be prepared without the need to grow them in a dish for several days, and it may not be necessary to take large volumes of blood or bone marrow from the patient - an advantage with respect to safety. In addition, cells from mice used to simulate atherosclerosis (mutant for a gene that helps clear fat from the blood and given a high fat diet) do not seem to lose their repair potential.

“Based on the insights gained from preclinical and clinical studies from several investigators, we view the use of CD31 positive cells as a second generation cardiovascular cell therapy that could be a novel option for the treatment of peripheral artery disease,” Yoon says.

He adds that CD31 positive cells may have potential for treating other conditions, including heart attack, heart failure and diabetic neuropathy, which his team is investigating in animal models.

The research was supported by the National Institutes of Health, the Department of Defense and the Korean Ministry of Education, Science and Technology.

Learn more about Emory’s health sciences: http://emoryhealthblog.com

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EAST LANSING, Mich. - MAY 18, 2010
Cholesterol crystals, known to be a catalyst for heart attacks and strokes, also cause cells to send out danger signals that can lead to the inflammation and hardening of arteries, according to a Michigan State University cardiologist.

George Abela, chief of the cardiology division in MSU’s College of Human Medicine. of Medicine Photos:news.msu.edu

The protruding elements seen in the different slides are cholesterol crystals. Those elements are arising from within the artery wall, causing tearing and damage to the artery. The colors have been added for enhancement and imagery.

The discovery by George Abela, chief of the cardiology division in MSU’s College of Human Medicine, and a team of researchers provides new insights into how arteries harden - a process called atherosclerosis - and gives hope for new and early treatments of cardiovascular disease.

The findings are published in the most recent edition of the journal Nature.

Past research has shown that as cholesterol builds up along the wall of an artery, it crystallizes from a liquid to a solid state and expands, said Abela, who has been studying cholesterol crystals for nearly a decade. As the crystals expand, they can disrupt plaque and cause clotting, leading to cardiac attacks. That research also was recently highlighted recently in the Journal of Clinical Lipidology.

In a new discovery, Abela and the team - while looking at causes of inflammation during atherosclerosis in mice - found that the once cholesterol crystals form in the arterial wall, they activate a biomarker called NLRP3 that induces inflammation.

“What we have found now, at the cellular level, is that the crystals are an early cause rather than a late consequence of inflammation,” Abela said.

The discovery could lead to new treatments for heart disease.

“Since cholesterol crystals form very early in the process of heart disease, with great potential to aggravate atherosclerosis, we can target them early on,” Abela said. “We can target new therapies by reducing cholesterol crystal deposits early on or use an inhibitor to block the inflammatory biomarker.”

Abela added that the biomarker activated by the crystals could be a better indicator of potential cardiovascular disease than others, such as serum cholesterol, or the amount of cholesterol found in the bloodstream.

“Now we treat atherosclerosis on the systematic level; with this discovery we can also treat it the cellular level,” he said.

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BUFFALO, N.Y. - MAY 3, 2010
Obesity, a condition linked to heart disease and diabetes, now appears to be associated with another health problem, but one that affects men only - low testosterone levels.

Sandeep Dhindsa, MD is an endocrinology specialist in the UB Department of Medicine of Medicine Photo:diabetes- endocrinologycenterofwny.com

Results of a study published online ahead of print in the journal Diabetes Care, conducted by University at Buffalo endocrinologists, showed that 40 percent of obese participants involved in the Hypogonadism in Males (HIM) study had lower than normal testosterone readings.

The percentage rose to 50 percent among obese men with diabetes. Results also revealed that as body mass index (BMI) - a relationship of weight to height - increased, testosterone levels fell.

“The effect of diabetes on lowering testosterone levels was similar to that of a weight gain of approximately 20 pounds,” says Sandeep Dhindsa, MD, an endocrinology specialist in the UB Department of Medicine and first author on the study.

“In view of the fact that almost one-third of the U.S. is obese, these observations have profound pathophysiological, clinical, epidemiological and public health implications.”

This is the largest analysis of the association between obesity and low testosterone, and the first to compare prevalence of low testosterone with obesity and diabetes separately and together. The study shows that obesity and diabetes may exert independent influences on testosterone concentrations.

“We published a report in 2004 on the high prevalence of low testosterone levels in men with type 2 diabetes, and multiple studies all over the world have confirmed the association of low testosterone with diabetes,” Dhindsa notes.

“The Endocrine Society now recommends that all men with type 2 diabetes should have their testosterone levels measured. Our new study shows that obese men also have a very high prevalence of low testosterone levels, so physicians should consider screening obese non diabetic men, as well, for low testosterone.”

The HIM study was funded by Solvay Pharmaceuticals Inc., and was conducted from November 2003 to February 2004 in 95 primary care practices throughout the U.S. The study involved 2,165 men 45 years or older who provided blood samples for analysis of testosterone concentrations.

UB researchers excluded participants from the full study who had no BMI data or were on certain drugs that can affect testosterone levels, providing a study population of 1,849 men - 398 with diabetes and 1,451 non diabetics.

“With the rising prevalence of obesity in the U.S. and the rest of the world,” says Paresh Dandona, MD, head of the Division of Endocrinology, Diabetes and Metabolism at UB and Kaleida Health, and senior author of the study, “it is imperative that the prevalence of low testosterone levels in obese men be defined. In addition, the magnitude of the contribution of obesity to subnormal testosterone needs to be quantified.

“We hypothesized that obese men are more likely to have low testosterone than non-obese men, and that we would find more low testosterone levels in men with diabetes than in men without diabetes, both obese and non obese.”

Results confirmed these hypotheses, showing a 40 percent higher prevalence of low testosterone in obese men compared to the non obese participants. Men with diabetes, whether obese or not, showed lower levels of testosterone than non diabetic men across all weight categories. Testosterone levels decreased significantly in both diabetic and non diabetic men as BMI increased.

“In view of the increasing prevalence of obesity, even in younger populations, it would be important to conduct a similar study in the men at the prime of their reproductive years,” he says.

UB endocrinologists published a study in Diabetes Care in 2008 showing that more than 50 percent of men between 18 and 35 years old with type 2 diabetes had lower than normal testosterone levels.

“In view of the high rates of subnormal testosterone in patients with obesity or diabetes, testosterone concentrations should be measured regularly in these populations, especially when these conditions occur together,” says Dandona.

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(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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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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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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TAU grows new blood vessels to combat heart disease

Although open-heart surgery is a frequent treatment for heart disease, it remains extremely dangerous. Now groundbreaking research from Dr. Britta Hardy of Tel Aviv University’s Sackler School of Medicine has shown the potential for an injected protein to regrow blood vessels in the human heart - eliminating the need for risky surgery altogether.

Dr. Britta Hardy

In heart disease, blood vessels are either clogged or die off, starving the heart of oxygen and leaving it highly susceptible to a cardiac attack. Dr. Hardy and her research partner Prof. Alexander Battler have developed a protein-based injection that, delivered straight to muscles in the body, sparks the regrowth of tiny blood vessels. These new vessels in the heart could give millions of people around the world a new lease on life.

Research on the procedure was recently published in Biochemical Pharmacology.

A treatment without side effects or inflammation

“The biotechnology behind our human-based protein therapy is very complicated, but the goal is simple and the solution is straightforward,” says Dr. Hardy. “We intend to inject our drug locally to heal any oxygen-starved tissue. So far in animal models, we’ve seen no side effects and no inflammation following our injection of the drug into the legs. The growth of new blood vessels happens within a few weeks, showing improved blood circulation.”

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WINSTON-SALEM, N.C. - A new study done by researchers at Wake Forest University School of Medicine shows that social stress could be an important precursor to heart disease by causing the body to deposit more fat in the abdominal cavity, speeding the harmful buildup of plaque in blood vessels, a stepping stone to the number one cause of death in the world. The findings could be an important consideration in the way the United States and other Western countries try to stem the rapid rise of obesity, said Carol A. Shively, Ph.D., a professor of pathology and the study’s principal investigator.

The study appears as the cover story of the current issue of Obesity, the peer-reviewed journal of the Obesity Society.

“We are in the midst of an obesity epidemic,” Shively said. “Much of the excess fat in many people who are overweight is located in the abdomen, and that fat behaves differently than fat in other locations. If there’s too much, it can have far more harmful effects on health than fat located in other areas.”

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Canadians of lower socioeconomic status at greatest risk The prevalence of heart disease and certain key risk factors - hypertension, diabetes, and obesity - are increasing in all age groups and most income groups in Canada found a new study published in CMAJ (Canadian Medical Association Journal) http://www.cmaj.ca/press/cmaj081629.pdf (www.cmaj.ca). This study, which looked at national data from 1994 to 2005, encompassed people aged 12 years and older sampling from Canadians of all socioeconomic and ethnic groups. Risk factors such as hypertension, diabetes, and obesity increased most rapidly among younger people between 12 to 50 years of age.

The study was conducted by researchers from the Institute for Clinical Evaluative Sciences, University Health Network, University of Toronto, Sunnybrook Health Sciences Centre, Toronto; Queen’s University, Kingston, Ontario; University of Alberta, University of Calgary, Alberta; Dalhousie University, Halifax, Nova Scotia; and Statistics Canada. It was funded by the Canadian Institutes of Health Research (CIHR).

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Landmark study from TAU shows how high carb foods cause heart attacks

Dr. Michael Shechter

Doctors have known for decades that foods like white bread and corn flakes aren’t good for cardiac health. In a landmark study, new research from Tel Aviv University now shows exactly how these high carb foods increase the risk for heart problems.

“Looking inside” the arteries of students eating a variety of foods, Dr. Michael Shechter of Tel Aviv University’s Sackler School of Medicine and the Heart Institute of Sheba Medical Center - with collaboration of the Endocrinology Institute - visualized exactly what happens inside the body when the wrong foods for a healthy heart are eaten. He found that foods with a high glycemic index distended brachial arteries for several hours.

Elasticity of arteries anywhere in the body can be a measure of heart health. But when aggravated over time, a sudden expansion of the artery wall can cause a number of negative health effects, including reduced elasticity, which can cause heart disease or sudden death.

Using a clinical and research technique pioneered by his laboratory in Israel, Dr. Shechter was able to visualize what happens inside our arteries before, during and after eating high carb foods. It is a first in medical history. The results were published in the Journal of the American College of Cardiology.

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(Santa Barbara, Calif.) - Scientists and engineers at UC Santa Barbara and other researchers have developed a nanoparticle that can attack plaque - a major cause of cardiovascular disease. The new development is described in a recent issue of the Proceedings of the National Academy of Sciences.

This is an image of a multifunctional micelle designed by research team. Peter Allen, UCSB College of Engineering

The treatment is promising for the eventual development of therapies for cardiovascular disease, which is blamed for one third of the deaths in the United States each year. Atherosclerosis, which was the focus of this study, is one of the leading causes of cardiovascular disease. In atherosclerosis, plaque builds up on the walls of arteries and can cause heart attack and stroke.

“The purpose of our grant is to develop targeted nanoparticles that specifically detect atherosclerotic plaques,” said Erkki Ruoslahti, distinguished professor at the Burnham Institute for Medical Research at the University of California, Santa Barbara. “We now have at least one peptide, described in the paper, that is capable of directing nanoparticles to the plaques.”

The nanoparticles in this study are lipid-based collections of molecules that form a sphere called a micelle. The micelle has a peptide, a piece of protein, on its surface, and that peptide binds to the surface of the plaque.

Co author Matthew Tirrell, The Richard A. Auhll Professor and dean of UCSB’s College of Engineering, specializes in lipid-based micelles. “This turned out to be a perfect fit with our targeting technology,” said Ruoslahti.

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Removing a single protein prevents early damage in blood vessels from triggering a later-stage, frequently lethal complication of atherosclerosis, according to research published online today in the journal Nature Medicine. By eliminating the gene for a signaling protein called cyclophilin A (CypA) from a strain of mice, researchers were able to provide complete protection against abdominal aortic aneurysm (AAA). The aorta is the main artery carrying blood from the heart, and AAA is a progressive outward dilation of the aorta under the stress of blood pressure due to a breakdown in the vessel’s structural integrity. AAA leads to 15,000 deaths a year, mostly in aging men, when aneurysms rupture to spill blood into the abdomen, a fatal event in 90 percent of cases. Adding to the study’s importance, AAA shares vital biochemical pathways with atherosclerosis, the leading cause of heart attack and stroke. Thus, drugs that target CypA could potentially address both AAA and atherosclerosis.When study mice were engineered to remove their CypA gene, none from that group developed AAA in the face of the hypertension and high cholesterol known to accelerate it. In contrast, 78 percent of mice with “normal” amounts of CypA developed AAA under the same conditions, 35 percent with a fatal rupture. The team also found high CypA levels in the rupture-prone vessels of humans with AAA, and that major drugs like statins reduce CypA levels, which may partly explain their benefit.

“It is extremely unusual for the removal of one protein to provide absolute protection, but it makes perfect sense because cyclophilin A promotes three of the most destructive forces in blood vessels - oxidative stress, inflammation and matrix degradation,” said Bradford C. Berk, M.D., Ph.D., professor of Medicine within the Aab Cardiovascular Research Institute at the University of Rochester Medical Center, and senior author of the study. “We are working to design anti-CypA drugs that will diminish the disease processes underlying AAA, atherosclerosis and hypertension.”

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Scientists have pinned down the constituent of olive oil that gives greatest protection from heart attack and stroke. In a study of the major antioxidants in olive oil, Portuguese researchers showed that one, DHPEA-EDA, protects red blood cells from damage more than any other part of olive oil. “These findings provide the scientific basis for the clear health benefits that have been seen in people who have olive oil in their diet,” says lead researcher Fatima Paiva-Martins, who works at the University of Porto.

Heart disease is caused partly by reactive oxygen, including free radicals, acting on LDL or “bad” cholesterol and resulting in hardening of the arteries. Red blood cells are particularly susceptible to oxidative damage because they are the body’s oxygen carriers.

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OTTAWA- Health Minister Leona Aglukkaq today announced that Canada continues to make progress towards reducing the amount of trans fat in the Canadian food supply. This data includes an analysis of bakery products, a small sample of international foods sold in restaurants, and nutrition information obtained from the Nutrition Facts table of prepackaged foods. According to new data released today from the trans fat monitoring program, 80% of the prepackaged foods selected for label review met the trans fat limit set by the Trans Fat Task Force in June 2006.

“Our government is pleased to see that industry has reduced the level of trans fat in many pre-packaged foods,” said Minister Aglukkaq. “This was achieved by finding healthier alternatives without increasing the levels of saturated fat. We are also encouraged that foods sold at various restaurants serving international cuisine are meeting the trans fat limit.”

The foods that were sampled in this set of data included:
- Bakery products from grocery stores, such as croissants, pies, tarts, cakes, brownies and donuts.
- Foods from restaurants serving Chinese, Thai, East Indian, Lebanese, Caribbean, Japanese and Vietnamese cuisines.
- Donuts and muffins from popular coffee and donut shops.
- Prepackaged foods from grocery stores, including cookies, crackers, instant noodles, frozen potatoes, desserts, snacks and popcorn.

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Only 3 percent of kids’ meals served at fast-food restaurants met federal dietary guidelines in the first study to examine the nutrient quality of such meals in a major U.S. metropolitan market. Michigan State University’s Sharon Hoerr, a food science and human nutrition researcher with the Michigan Agricultural Experiment Station, teamed up with economist Sharon O’Donnell and pediatrician Jason Mendoza from Baylor College of Medicine in Houston to assess the nutritional status of kids’ meals in the Houston market.The small percentage of meals that did meet dietary guidelines included fruit as a side dish and milk, and nearly all were deli-sandwich meals. They also had about one-third the fat, one-sixth the added sugars, twice the iron and three times the amount of vitamin A and calcium as did meals not meeting the criteria.

“This report is the first to characterize and compare the nutrient quality of all combinations of fast-food kids’ meals in a major metropolitan market,” Hoerr said. “Because 25 percent of children aged 4 to 8 years consume fast food on a typical day, the diet quality of kids’ meals offered by fast-food companies contributes significantly to their overall health and well-being.

“Two trends motivate the need for an evaluation of the nutrient quality of fast-food kids’ meals: the increased prevalence of childhood obesity and the amount of food consumed away from home.”

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