‘Genetic doppelgangers:’ Emory research provides insight into two neurological puzzles

An international team led by Emory scientists has gained insight into the pathological mechanisms behind two devastating neurodegenerative diseases. The scientists compared the most common inherited form of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) with a rarer disease called spinocerebellar ataxia type 36 (SCA 36). Both of the diseases are caused by abnormally expanded and strikingly similar DNA repeats. However, ALS progresses quickly, typically killing patients within a year or two, while the disease Read more

Emory launches study on COVID-19 immune responses

Emory University researchers are taking part in a multi-site study across the United States to track the immune responses of people hospitalized with COVID-19 that will help inform how the disease progresses and potentially identify new ways to treat it.  The study is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The study – called Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) – launched Friday. Read more

Marcus Lab researchers make key cancer discovery

A new discovery by Emory researchers in certain lung cancer patients could help improve patient outcomes before the cancer metastasizes. The researchers in the renowned Marcus Laboratory identified that highly invasive leader cells have a specific cluster of mutations that are also found in non-small cell lung cancer patients. Leader cells play a dominant role in tumor progression, and the researchers discovered that patients with the mutations experienced poorer survival rates. The findings mark the first Read more

cardiology

Epigenetic changes in atherosclerosis

If someone living in America and eating a typical diet and leading a sedentary lifestyle lets a few years go by, we can expect plaques of cholesterol and inflammatory cells to build up in his or her arteries. We’re not talking “Super-size Me” here, we’re just talking average American. But then let’s say that same person decides: “OK, I’m going to shape up. I’m going to eat healthier and exercise more.”

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Let’s leave aside whether low-carb or low-fat is best, and let’s say that person succeeds in sticking to his or her declared goals. How “locked in” are the changes in the blood vessels when someone has healthy or unhealthy blood flow patterns?

Biomedical engineer Hanjoong Jo and his colleagues published a paper in Journal of Clinical Investigation that touches on this issue. They have an animal model where disturbed blood flow triggers the accumulation of atherosclerosis. They show that the gene expression changes in endothelial cells, which line blood vessels, have an epigenetic component. Specifically, the durable DNA modification known as methylation is involved, and blocking DNA methylation with a drug used for treating some forms of cancer can prevent atherosclerosis in their model. This suggests that blood vessels retain an epigenetic imprint reflecting the blood flow patterns they see.

Although treating atherosclerosis with the drug decitabine is not a viable option clinically, Jo’s team was able to find several genes that are silenced by disturbed blood flow and that need DNA methylation to stay shut off. A handful of those genes have a common mechanism of regulation and may be good therapeutic targets for drug discovery.

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Thyroid makes young mouse hearts grow

The entire heart muscle in young children may hold untapped potential for regeneration, new research suggests.

For decades, scientists believed that after a child’s first few days of life, cardiac muscle cells did not divide. Instead, the assumption was that the heart could only grow by having the muscle cells become larger.

Cracks were already appearing in that theory. But new findings in mice, published May 8 in Cell, provide a dramatic counterexample — with implications for the treatment of congenital heart disorders in humans. Read more

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Packaging stem cells in capsules for heart therapy

Stem cell therapy for heart disease is happening. Around the world, thousands of heart disease patients have been treated in clinical studies with some form of bone marrow cells or stem cells. But in many of those studies, the actual impact on heart function was modest or inconsistent. One reason is that most of the cells either don’t stay in the heart or die soon after being introduced into the body.

Cardiology researchers at Emory have a solution for this problem. The researchers package stem cells in a capsule made of alginate, a gel-like substance. Once packaged, the cells stay put, releasing their healing factors over time.

Researchers used encapsulated mesenchymal stem cells to form a “patch” that was applied to the hearts of rats after a heart attack. Compared with animals treated with naked cells (or with nothing), rats treated with the capsule patches displayed increased heart function, reduced scar size and more growth of new blood vessels a month later. In addition, many more of the encapsulated cells stayed alive. Read more

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Molecular beacons shine path to cardiac muscle repair

Pure cardiac muscle cells, ready to transplant into a patient affected by heart disease.

That’s a goal for many cardiology researchers working with stem cells. Having a pure population of cardiac muscle cells is essential for avoiding tumor formation after transplantation, but has been technically challenging.

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Fluorescent beacons that distinguish cardiac muscle cells

Researchers at Emory and Georgia Tech have developed a method for Cheap Oakleys purifying cardiac muscle cells from stem cell cultures using molecular beacons.

Molecular beacons are tiny “instruments” that become fluorescent only when they find cells that have turned on certain genes. In this case, they target instructions to make a type of myosin, a protein found in cardiac muscle cells.

Doctors could use purified cardiac muscle cells to heal damaged areas of the heart in patients affected by heart attack and heart failure. In addition, the molecular beacons technique http://www.lependart.com could have broad applications across regenerative medicine, because it could be used with other types of cells produced from stem cell cultures, such as brain cells or insulin-producing islet cells.

The results are published in the journal Circulation.

“Often, we want to generate a particular cell population from stem cells for introduction into patients,” says co-senior author Young-sup Yoon, MD, PhD, professor of medicine (cardiology) and director of stem cell biology at Emory University School of Medicine. “But the desired cells often lack a readily accessible surface marker, or that marker is not specific enough, as is the case for cardiac muscle cells. This technique could allow us to purify almost any type of cell.”

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FAME 2 clarifies benefits of coronary stents

Who should get stents, the tiny metal tubes designed to keep clogged coronary arteries open? Someone who is having a heart attack certainly should, and the life-prolonging benefits have been demonstrated in several studies. But results have been more ambiguous for patients who have “stable angina”: chest pain that comes with exertion but goes away at rest.

Kreton Mavromatis, MD

A recent study addressing this topic called FAME 2 has received extensive media coverage. It was published in the New England Journal of Medicine and also presented at the European Society of Cardiology meeting in Munich. Kreton Mavromatis, MD, director of cardiac catheterization at the Atlanta VA Medical Center and assistant professor of medicine at Emory, was a co-author on the NEJM paper.

In the new study, researchers used a technique called fractional flow reserve (FFR) to decide if someone with stable angina should get a stent, or receive medical therapy with drugs such as aspirin and statins. Conventionally, X-ray coronary angiography is used to assess the need for a stent.

FFR involves introducing a pressure sensor via guidewire into the coronary artery, to measure how much blood flow is being blocked. FAME 2 was sponsored by St Jude Medical, a company that makes guidewire equipment for use in FFR.

Fractional flow reserve is a way of assessing the effects of blockages in blood flow in a coronary artery.

The clinical trial was stopped early because of clear differences in the rates of hospitalization (4 percent for stents against 13 percent for medical therapy)

“FAME 2 showed that the strategy of treating stable ischemic heart disease with FFR-guided coronary stenting reduces the combination of death, MI and urgent revascularization as compared with strategy of medical therapy alone,” Mavromatis says. “This benefit was specifically due to the reduced need of urgent revascularization due to acute coronary syndrome, a dramatic event for our patients.”

Some cardiologists have criticized the FAME 2 study, noting that the benefits of stenting didn’t come in terms of reducing “hard events” (deaths and heart attacks).

“It is important to recognize that less symptoms of angina and less chance of hospitalization are tremendous benefits that our patients really appreciate,” Mavromatis says. “I think FFR will play a bigger role in evaluating and treating coronary artery disease, as it can direct stenting much more precisely than angiography toward clinically important coronary artery disease, improving patients’ outcomes and saving money.”

The FFR procedure costs several hundred dollars but that is significantly less than the cost of implanting a coronary stent. Habib Samady, MD, director of interventional cardiology at Emory, has also been an advocate for the use of FFR to select who would benefit from a coronary stent. He wrote an article describing its uses in 2009:

We have been using and advocating FFR since pressure guidewire technology first came to the U.S. in 1998. At Emory, we are sometimes asked to reevaluate patients who have been slated for CABG surgery at another hospital where recommendations are made based on angiography alone. When we evaluate these cases using FFR, we are sometimes able to recommend courses of treatment that involve fewer stents or even medical therapy. Occasionally, based on FFR data, we send our patients for an endoscopic or “minimally invasive” bypass and stent the remaining narrowings.

In addition, FFR has helped reduce the number of multi-vessel PCIs performed. Patients who might have received stents in three vessels after angiography alone would likely receive stents in only one or two vessels after FFR-guided analysis. Among patients with single-vessel disease, FFR often has allowed us to recommend medical treatment in lieu of stenting. Implanting fewer stents also means using less contrast agent and fewer materials, which lowers the expenses involved in treatment.

A large, multi-center study called ISCHEMIA is starting that will address the coronary stent vs medical therapy issue in a more definitive way. Both Emory and the Atlanta VA Medical Center are participating. “This is a very important next step in understanding the benefits of invasive therapy of stable ischemic heart disease,” Mavromatis says.

 

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Emory cardiologist weighs in on issue of health literacy

Javed Butler, MD, MPH

A story in yesterday’s edition of the Washington Post claims that many Americans have poor health literacy. The Post cited a 2006 study by the U.S. Department of Education that found that 36 percent of adults have only basic or below-basic skills for dealing with health material. According to the report, this means about 90 million Americans can understand discharge instructions written only at a fifth-grade level or lower.

Emory Healthcare heart transplant cardiologist, Javed Butler, MD, MPH, was included in yesterday’s Post article citing his experience with patients who have health literacy issues. “When we say ‘diet,’ we mean ‘food,’ but patients think we mean going on a diet,” said Butler. “And when we say ‘exercise,’ we may mean ‘walking,’ but patients think we mean ‘going to the gym.’ At every step there’s a potential for misunderstanding.”

Butler, a professor of medicine at the Emory School of Medicine and director of Heart Failure Research for Emory Healthcare is studying this issue and its impact on patients with heart failure. He recently reported some of his findings Nov. 17 at the American Heart Association Scientific Sessions conference in Chicago.

To read the entire Washington Post story, please click here.

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Clinical trial for patients with atrial fibrillation tests implantable device in place of blood-thinning drug

Clinical Trial for Patients with A-fib

A new clinical trial underway for patients with atrial fibrillation will test an implantable device in place of a common blood-thinning medication, according to researchers at Emory University Hospital Midtown.

Atrial fibrillation (commonly called A-fib) is a heart condition in which the upper chambers of the heart beat too fast, causing an irregular heartbeat and ineffective pumping action. This condition can cause blood to pool and form clots in the left atrial appendage (LAA). If a clot forms in this area, it can increase the chances of having a stroke.

Many patients with A-fib are prescribed blood-thinning medications, such as warfarin (brand name Coumadin), to prevent blood from clotting. This medication is effective in reducing the risk of stroke, but may cause side effects such as bleeding. It also requires frequent blood draws to monitor dosage levels.

The trial, called PREVAIL (Prospective Randomized EVAluation of the Watchman LAA Closure Device In Patients with Atrial Fibrillation Versus Long Term Warfarin Therapy), involves implanting a small, umbrella-shaped mesh device called the Watchman closure device, into the heart chamber via catheter. This is a confirmatory study (and the third study testing the implant), which will also look at safety and efficacy of the device.

David De Lurgio, MD, associate professor of medicine in the Division of Cardiology, Emory University School of Medicine, is the principal investigator of the trial. He explains that by implanting this device into the left atrial appendage of the heart, it closes that area off. That, in turn, prevents blood clots from escaping and entering the blood stream, which could lead to a stroke.

Patients are randomly selected by computer to either receive the device or remain on Coumadin without the device (control group). Those selected to receive the device will remain on Coumadin for 45 days following implant. If the heart tissue has healed after those 45 days, participants will be taken off Coumadin and placed on aspirin therapy and possibly clopidogrel (Plavix), an anti-platelet medication.

Researchers will then follow study patients with and without the device for five years, monitoring those who are no longer taking Coumadin very closely. If the FDA approves the device at the end of this clinical trial, participants in the control group will then have the option to receive the device.

De Lurgio and his colleagues have had five years of experience with this technology, thus far. Emory Healthcare is the only health system in Georgia providing access to this device through participation in this clinical trial.

For more information, please call 404-686-2504.

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A good reason to enjoy a little Valentine’s Day chocolate

From the Clinic to You

BY CHERYL WILLIAMS, RD, LD

If you’re looking for an excuse to indulge in the yummy chocolate you get this Valentine’s Day, research suggests it may not be so bad for you.

A number of studies, conducted over the last decade have associated cocoa and dark chocolate consumption with heart health benefits. These benefits come from cocoa, derived from the cacao plant, which is rich in flavonoids (cocoa flavanols to be exact). Flavonoids are antioxidants also found in berries, grapes, tea, and apples. As a whole, antioxidants prevent cellular damage and inflammation which are two major mechanisms involved in the development of heart disease.

So what does the research say?

A study published in the American Journal of Clinical Nutrition found that high-flavanol dark chocolate reduced bad cholesterol (LDL) oxidation and increased good cholesterol (HDL) levels. LDL oxidation promotes the development of plaque and hardening of the coronary arteries, thus lessening oxidation could help to prevent heart disease.

A Harvard research study found that flavanol-rich cocoa induced nitric-oxide production, which causes blood vessels to relax and expand, thus improving blood flow. Improved coronary vasodilation could potentially lower the risk of a cardiovascular event.

In a double-blind randomized Circulation study flavonoid-rich dark chocolate (containing 70% cocoa) reduced serum oxidative stress and decreased platelet activity (clumping) in heart transplant recipients. This favorable impact on vascular and platelet function is relevant because vascular dysfunction and platelet activation (adhesion upon damaged cell wall) are the basis of atherothrombosis (blood clotting) and coronary artery disease.

How can you reap chocolate’s potential benefits?

Not all cocoa products and/or chocolates are created equal. Milk chocolate, for example, is not rich in flavanols (contains only 10-20% cocoa solids) and white chocolate contains none at all. In addition, some cocoa products and chocolates are processed with alkali, which can destroy flavanols.

Follow these tips for heart healthy chocolate consumption:

  • Avoid cocoa products processed with alkali (dutched) as seen in the ingredient list
  • Choose dark chocolate with at least 70% cocoa
  • Enjoy 100% unsweetened non-dutched cocoa (great for hot chocolate!)

Also, remember that chocolate is not a health food, as it is high in calories, fat and added sugar. Thus, make room for dark chocolate by cutting extra calories elsewhere in your diet. Additionally, stick to small amounts (e.g. 1 ounce) and do not eat in place of plant-based whole foods such as vegetables and fruits.

Cheryl Williams is a registered dietitian at the Emory Heart & Vascular Center. She provides nutrition therapy, wellness coaching, monthly nutrition seminars and healthy cooking demonstrations working with the Emory HeartWise Cardiac Risk Reduction Program.

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A path to treatment of lymphedema

Lymphedema, or swelling because of the impaired flow of lymph fluid, can occur as a consequence of cancer or cancer treatment. Chemotherapy can damage lymph ducts, and often surgeons remove lymph nodes that may be affected by cancer metastasis. Lymphedema can result in painful swelling, impaired mobility and changes in appearance.

Young-sup Yoon, MD, PhD

Emory scientists, led by cardiologist and stem cell biologist Young-sup Yoon, have shown that they can isolate progenitor cells for the lining of lymph ducts. This finding could lead to doctors being able to regenerate and repair lymph ducts using a patient’s own cells. The results are described in a paper published recently in the journal Circulation.

The authors used the cell surface marker podoplanin as a handle for isolating the progenitor cells from bone marrow. Previous research has demonstrated that podoplanin is essential for the development of the lymphatic system.
In the paper, the authors use several animal models to show that the progenitor cells could contribute to the formation of new lymph ducts, both by becoming part of the lymph ducts and by stimulating the growth of nearby cells.

“This lymphatic vessel–forming capability can be used for the treatment of lymphedema or chronic unhealed wounds,” Yoon says.

Isolated lymphatic endothelial cells (red) incorporate into lymph ducts (green) in a model of wound healing in mice.

The authors also show that mice with tumors show an increase in the number of this type of circulating progenitor cells. This suggests that tumors send out signals that encourage lymph duct growth – a parallel to the well-known ability of tumors to drive growth of blood vessels nearby. Yoon says the presence of these cells could be a marker for tumor growth and metastasis. Because tumors often metastasize along lymph ducts and into lymph nodes, studying this type of cells could lead to new targets for blocking tumor metastasis.

A recent review in the journal Genes & Development summarizes additional functions of the lymphatic system in fat metabolism, obesity, inflammation, and the regulation of salt storage in hypertension.

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Higher education linked to improved heart disease outcomes in richer countries

A higher level of education is associated with reduced risk of heart disease and stroke for people who live in rich countries, but not for those in low- and middle-income nations, according to the findings of a recent study led by Emory epidemiologist and cardiologist Abhinav Goyal, MD, MHS.

Abhinav Goyal, MD, MHS

The study published in the Sept. 7, 2010, issue of the journal Circulation, a publication of the American Heart Association, is one of the first international studies to compare the link between formal education and heart disease and stroke. It examined data on 61,332 people from 44 countries who had been diagnosed with heart disease, stroke, or peripheral arterial disease, or who had cardiovascular disease risk factors such as smoking or obesity.

Goyal and team found that highly educated men in high-income countries had the lowest level of cardiovascular disease. However, their findings suggest that research conducted in richer nations can’t always be applied to poorer countries.

“We can’t simply take studies that are conducted in high-income countries, particularly as they relate to socioeconomic status and health outcomes, and extrapolate them to low- and middle-income countries,” says Goyal, assistant professor of epidemiology and cardiology at Emory’s Rollins School of Public Health and Emory School of Medicine. “We need dedicated studies in those settings.”

The research team was surprised to find that despite decreased heart disease risk among the higher educated in industrialized nations, nearly half of the highly educated women from high-income countries smoked, compared with 35 percent for those with the least amount of schooling. For men, smoking rates were virtually the same across educational groups in low- and middle-income countries.

“Everyone needs to be educated about the risk of heart disease in particular, and counseled to adopt healthy lifestyles and to quit smoking,” Goyal says.

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