On Thursday, cardiology researcher Leslee Shaw, PhD joined an exclusive club at Emory with her 2015 Deanâ€™s Distinguished Faculty Lecture and Award.* Shaw is the co-director of Emoryâ€™s Clinical Cardiovascular Research Institute and research director of Emory Womenâ€™s Heart Center. Her lecture focused on the utility of coronary artery calcium (CAC) scoring in predicting cardiovascular disease.
Much cardiovascular risk research has focused on finding imaging or biomarker tests that can provide doctors with cost-effective decision-making power. OneÂ prominent question: should the patient take cholesterol-reducing statins? These tests should provide information above and beyond the Framingham Risk Score or its ACC/AHA update, which incorporates information about a patientâ€™s age, sex, cholesterol/HDL, blood pressure and diabetes status.
CAC scoring is a good place to start, Shaw said, since it is a standardized, relatively inexpensive test that measures the buildup of calcium in atherosclerotic plaque, and the radiation dose is low compared with other cardiac imaging techniques. Read more
It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After divertingÂ some of these topics into the 2015 crystal ball
,Â I corralledÂ them into themes.
1. Cardiac cell therapy
2. Mobilizing the body’s own regenerative potential
4. Parkinson’s disease therapeutic strategies
(Gary Miller, better packaging for dopamine could avoidÂ stress to neurons).
5. Personal genomics/exome sequencing
, likeÂ Emory’s Robert Gross
and Costas Hadjpanayis, do amazing things
7. Fun vsÂ no fun
Our Web expert
tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
Patients who receive more cells get significant benefits. That’s a key lesson emerging from a clinical trial that was reported this week at the American Heart Association meeting in Chicago.
In this study, doctors treated heart attack patients with their own bone marrow cells, selected for their healing potential and then reinjected into the heart, in an effort to improve the heart’s recovery. In the PreSERVE-AMI phase II trial, physicians from 60 sites (author list) treated 161 patients, making the study one of the largest to assess cell therapy for heart attacks in the United States. The study was sponsored by NeoStem, Inc.
“This was an enormous undertaking, one that broke new ground in terms of assessing cell therapy rigorously,” says the study’s principal investigator, Arshed Quyyumi, MD, professor of medicine at Emory University School of Medicine and co-director of the Emory Clinical Cardiovascular Research Institute. “We made some real progress in determining the cell type and doses that can benefit patients, in a group for whom the risks of progression to heart failure are high.” Read more
Cardiologist Bob Taylor and colleagues have a new paper in PLOS One this week, looking at the biomechanical forces behind plaque erosion.
Plaque erosion is a mechanism for blood clots formation in coronary arteries that is not as well-understood as its more explosive counterpart, plaque rupture. Plaque erosion disproportionally affects women more than men and is thought to account for most heart attacks in younger women (women younger than 50).
“We believe that this work has implications for our better understanding of the underlying biology of coronary artery disease in women,” Taylor says. The first author of the paper is biomedical engineering graduate student Ian Campbell, who now has his PhD. The team collaborated with cardiovascular pathologist Renu Virmani in Maryland.
Cardiologists have well-developed ideas for how plaque rupture works*; see the concept of vulnerable plaque. Cholesterol and inflammatory cells build up in the coronary arteries over several years. At one point in a particular artery, the plaque has a core of dying inflammatory cells, covered by a fibrous cap. If the cap is thin (the patterns of blood flows near the cap influence this), there is a risk that the cap will break and the contents of the core will spill out, triggering a blood clot nearby.
Plaque erosion is more mysterious and can occur more gradually, the researchers have found. Read more
Biomedical engineer Mike Davis reports he has obtained NHLBI funding to look into therapeutic applications of exosomes in cardiology. But wait. What are exosomes? Time for an explainer!
Exosomes are tiny membrane-wrapped bags, which form inside cells and are then spat out. Theyâ€™re about 100 or 150 nanometers in diameter. Thatâ€™s smaller than the smallest bacteria, and about as large as a single influenza or HIV virion. Theyâ€™re not visible under a light microscope, but are detectable with an electron microscope.
Scientific interestÂ in exosomes shot up after it was discovered that they can contain RNA, specifically microRNAs, which inhibit the activity of other genes. This could be another way in which cells talk to each other long-distance, besides secreting proteins or hormones. Exosomes are thus something like viruses, without the infectivity.
Since researchers are finding that microRNAs have potential as therapeutic agents, why not harness the vehicles that cells use to send microRNAs to each other? Similarly, if so much evidence points toward the main effect of cell therapy coming from what the cells make rather than the cells themselves, why not simply harvest what the cells make? Read more
If someone living in America and eating a typical diet and leading a sedentary lifestyleÂ 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 healthierÂ and exercise more.”
Let’s leave asideÂ 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 vesselsÂ when someone has healthy or unhealthy blood flow patterns?
Biomedical engineer Hanjoong Jo and his colleagues published aÂ 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.Â Specifically, the durable DNA modification known asÂ methylation is involved, and blocking DNA methylation with a drug used for treating some forms of cancer can prevent atherosclerosis in their model.Â This suggests that blood vessels retain an epigenetic imprint reflecting the blood flow patterns they see.
Although treating atherosclerosis with theÂ drug decitabine is notÂ a viable option clinically, Jo’s team was able to find severalÂ genes that are silenced by disturbed blood flow and that need DNA methylation to stay shut off. A handful of thoseÂ genes have aÂ common mechanism of regulationÂ and may be good therapeutic targets for drug discovery.
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.
CracksÂ were alreadyÂ appearingÂ in that theory. But new findings in mice, published May 8 inÂ Cell, provide a dramatic counterexample — with implications for the treatment of congenital heart disorders in humans. Read more
Posted on May 19, 2014
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 donâ€™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 â€œpatchâ€ 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
Pure cardiac muscle cells, ready to transplant into a patient affected by heart disease.
Thatâ€™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.
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.”