Exosomes as potential biomarkers of radiation exposure

Exosomes = potential biomarkers of radiation in the Read more

Before the cardiologist goes nuclear w/ stress #AHA17

Measuring troponin in CAD patients before embarking on stress testing may provide Read more

Virus hunting season open

Previously unknown viruses, identified by Winship + UCSF scientists, come from a patient with a melanoma that had metastasized to the Read more

cardiology

Microgravity means more cardiac muscle cells

Cardiac muscle cells derived from stem cells could eventually be used to treat heart diseases in children or adults, reshaping hearts with congenital defects or repairing damaged tissue.

srep30956-f2

Cardiomyocytes produced with the help of simulated microgravity. Red represents the cardiac muscle marker troponin, and green is cadherin, which helps cells stick to each other. Blue = cell nuclei. From Jha et al SciRep (2016).

Using the right growth factors and conditions, it is possible to direct pluripotent stem cells into becoming cardiac muscle cells, which form spheres that beat spontaneously. Researchers led by Chunhui Xu, PhD, director of the Cardiomyocyte Stem Cell Laboratory in Emory’s Department of Pediatrics, are figuring out how to grow lots of these muscle cells and keep them healthy and adaptable.

As part of this effort, Xu and her team discovered that growing stem cells under “simulated microgravity” for a few days stimulates the production of cardiac muscle cells, several times more effectively than regular conditions. The results were published on Friday, Aug. 5 in Scientific Reports. The first author of the paper is postdoctoral fellow Rajneesh Jha, PhD. Read more

Posted on by Quinn Eastman in Heart Leave a comment

Focal adhesions in Technicolor

i-QMq63rH-S

Mouse embryonic fibroblasts forming focal adhesions

Congratulations to Alejandra Valdivia, PhD, winner of the Best Image contest held as part of the Emory Postdoctoral Research Symposium, which takes place next week (Thursday, May 19). She is in Alejandra San Martin’s lab, studying NADPH oxidase enzymes and how they regulate cell migration.

Valdivia submitted this image of mouse embryonic fibroblasts forming focal adhesions, points of contact of the cell with the extracellular matrix. Focal adhesions allow the cells to adhere and migrate.

Explanation: Red is for paxillin, a protein concentrated in focal adhesions. Green is phalloidin, a toxin from mushrooms that binds one type of the cytoskeletal protein actin, seen here as stress fibers. Blue is DNA, showing the cells’ nuclei.

 

Posted on by Quinn Eastman in Heart Leave a comment

Football metabolomics

Following on the recent announcement of the Atlanta Hawks training center, here’s a Nov. 2015 research paper from Emory’s sports cardiologist Jonathan Kim, published in Annals of Sports Medicine and Research.

Jonathan Kim, MD

Kim and colleagues from Emory Clinical Cardiovascular Research Institute studied blood samples from 15 freshman football players at Georgia Tech before and after their first competitive season. The researchers had the help of metabolomics expert Dean Jones. Kim has also previously studied blood pressure risk factors in college football players.

On average, football players’ resting heart rate went down significantly (72 to 61 beats per minute), but there were no significant changes in body mass index or blood pressure. The research team observed changes in players’ amino acid metabolism, which they attribute to muscle buildup.

This finding may seem obvious, but imagine what a larger, more detailed analysis could do: start to replace locker room myths and marketing aimed at bodybuilders with science. This was a small, preliminary study, and the authors note they were not able to assess diet or nutritional supplementation. Read more

Posted on by Quinn Eastman in Heart Leave a comment

Food deserts and cardiovascular risk

Heval Mohamed Kelli, MD got some attention at the American College of Cardiology meeting over the weekend with his work on food deserts — low-income areas distant from access to healthy food.

As Medscape summarized the results: “Atlantans living in disadvantaged areas where the nearest supermarket was a mile or more away were more likely to have hypertension or hyperlipidemia, smoke, be obese, and have higher levels of systemic inflammatory markers and stiffer arteries.”

Kelli_cover

Kelli at Clarkston Health Clinic, which Emory doctors helped establish in 2015. Clarkston is considered a “food desert”.

For more on Kelli’s journey from Syrian refugee to Clarkston, GA teenager to Emory cardiology researcher, check out this feature in Emory Magazine.

His research was conducted through the Emory Clinical Cardiovascular Research Institute, using information on 712 community participants from the META-Health study and 709 Emory/Georgia Tech employees from the Predictive Health study.

Three possibilities for further investigation:

*Income, education, race and geography are intertwined. “Whether lack of access to healthy foods, low income, or low education is driving these processes needs to be further studied,” Kelli and colleagues concluded.

*For detailed maps of food deserts, not just in Atlanta and/or determined using different criteria, the U.S. Department of Agriculture makes it possible.

*This Atlantic article makes the point that “when it comes to nutrition access, the focus should be on poverty, not grocery-store location.” You can lead people to the supermarket (or build one close to where they live), but you can’t make them eat a Mediterranean diet. Studies from Los Angeles showed that obesity increased more in some neighborhoods, even despite a ban on new fast food restaurants.

Posted on by Quinn Eastman in Heart Leave a comment

When cardiac risk biomarkers will become really useful (and save money?)

The news is awash in studies of cholesterol-lowering statins and a much-anticipated (and expensive) class of drugs called PCSK9 inhibitors. Clinical trials show that now-generic (and cheap) statins reduce the risk of heart attack and stroke, although some patients report they can’t tolerate them. The data is still to come showing whether PCSK9 inhibitors have the same risk-lowering effect, as opposed to their effects on LDL cholesterol, which are robust.

When /if doctors have to start deciding who should take drugs that cost thousands of dollars a year and who shouldn’t, biomarkers may come in handy. How about a panel of markers like the one studied by Emory cardiologist Arshed Quyyumi, MD and colleagues?

At the recent American College of Cardiology meeting in Chicago, research fellow Salim Hayek, MD reported on a five-marker panel and how it could predict the risk of cardiovascular events (that is: death, heart attack, hospitalization for heart failure) in a group of patients who underwent cardiac catheterization at Emory hospitals.

The five biomarkers are: C-reactive protein (CRP, measures inflammation), suPAR (soluble urokinase-type plasminogen activator receptor or suPAR, predicts kidney disease), fibrin degradation products (FDP: blood coagulation), heat-shock protein-70 (HSP70, cellular stress) and troponin (hs-TnI, cardiac muscle damage). Data on three of these were published in 2013.

The Emory team keeps adding more biomarkers, and the ability of the accumulated information to add to what doctors can figure out easily — the Framingham score and its successors — becomes stronger.

Posted on by Quinn Eastman in Heart Leave a comment

ACC 2016: Stem cell study sees improved heart failure outcomes

Patients with heart failure who received an experimental stem cell therapy experienced a reduced rate of death, hospitalization and unplanned clinic visits over the next year compared to a placebo group, according to results presented Monday at the American College of Cardiology meeting in Chicago.

The results of the ixCELL-DCM study were published online Monday by The Lancet. It was reportedly the largest cell therapy study done in patients with heart failure so far (58 treated vs 51 placebo).

Emory University School of Medicine investigators led by Arshed Quyyumi, MD, and their patients participated in the study, and Emory was one of the largest enrolling sites. Lead authors were Timothy Henry, MD of Cedars-Sinai Heart Institute in Los Angeles and Amit Patel, MD of the University of Utah.

“For the first time, a clinical trial has shown that administration of a cellular therapeutic results in an improvement in cardiac outcomes based on a prespecified analysis,” an editorial accompanying the paper in The Lancet says.

This study, which was sponsored by Vericel Corporation, was phase II, meaning that a larger phase III study will be needed before FDA approval. Read more

Posted on by Quinn Eastman in Heart Leave a comment

ACC 2016: Elevated troponin linked to mental stress ischemia

Some people with heart disease experience a restriction of blood flow to the heart in response to psychological stress. Usually silent (not painful), the temporary restriction in blood flow, called ischemia, is an indicator of greater mortality risk.

Cardiologists at Emory University School of Medicine have discovered that people in this group tend to have higher levels of troponin — a protein whose increased presence in the blood that is a sign of recent damage or stress to the heart muscle– all the time, independently of whether they are experiencing stress or chest pain at that moment.

The results were presented Sunday by cardiology research fellow Muhammad Hammadah, MD at the American College of Cardiology meeting in Chicago, as part of the Young Investigator Awards competition. Hammadah works with Arshed Quyyumi, MD, and Viola Vaccarino, MD, PhD, and colleagues at the Emory Clinical Cardiovascular Research Institute.

“Elevated troponin levels in patients with coronary artery disease may be a sign that they are experiencing repeated ischemic events in everyday life, with either psychological or physical triggers,” Hammadah says.

Doctors test for troponin in the blood to tell whether someone has recently had a heart attack. But the levels seen in this study were lower than those used to diagnose a heart attack: less than a standard cutoff of 26 picograms per milliliter, in a range that only a high-sensitivity test for troponin could detect.

In a separate study, Emory investigators have shown that elevated troponin levels (especially: more than 10 pg/mL)  predict mortality risk over the next few years in patients undergoing cardiac catheterization, even in those without apparent coronary artery disease.

There is already a lot of information available for doctors about the significance of elevated troponin. It has even been detected at elevated levels after strenuous exercise in healthy individuals. One recent study suggested that low levels of troponin could be used to rule out heart attack for patients in the emergency department.

More information about the mental stress ischemia study: Read more

Posted on by Quinn Eastman in Heart Leave a comment

Emory labs on LabTV

This summer, video producers from the web site LabTV came to two laboratories at Emory. We are pleased to highlight the first crop of documentary-style videos.

LabTV features hundreds of young researchers from universities and institutes around the United States, who tell the public about themselves and their research. The videos include childhood photos and explanations from the scientists about what they do and what motivates them. Screen Shot 2015-12-18 at 9.14.51 AM

The two Emory labs are: Malu Tansey’s lab in the Department of Physiology, which studies the intersection of neuroscience and immunology, focusing on neurodegenerative disease, and Mike Davis’ lab in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, which is developing regenerative approaches and technologies for heart disease in adults and children. Read more

Posted on by Quinn Eastman in Heart, Immunology, Neuro Leave a comment

CV cell therapy: bridge between nurse and building block

In the field of cell therapy for cardiovascular diseases, researchers see two main ways that the cells can provide benefits:

*As building blocks – actually replacing dead cells in damaged tissues

*As nurses — supplying growth factors and other supportive signals, but not becoming part of damaged tissues

Tension between these two roles arises partly from the source of the cells.

Many clinical trials have used bone marrow-derived cells, and the benefits here appear to come mostly from the “paracrine” nurse function. A more ambitious approach is to use progenitor-type cells, which may have to come from iPS cells or cardiac stem cells isolated via biopsy-like procedures. These cells may have a better chance of actually becoming part of the damaged tissue’s muscles or blood vessels, but they are more difficult to obtain and engineer.

A related concern: available evidence suggests introduced cells – no matter if they are primarily serving as nurses or building blocks — don’t survive or even stay in their target tissue for long.

Transplanted cells were labeled with a red dye, while a perfused green dye shows the extent of functional blood vessels. Blue is DAPI, staining nuclear DNA. Yellow arrows indicate where red cells appear to contribute to blood vessels.

Transplanted cells were labeled with a red dye, while a perfused green dye shows the extent of functional blood vessels. Blue is DAPI, staining nuclear DNA. Yellow arrows indicate where red cells appear to contribute to green blood vessels. Courtesy of Sangho Lee.

Stem cell biologist Young-sup Yoon and colleagues recently published a paper in Biomaterials in which the authors use chitosan, a gel-like carbohydrate material obtained by processing crustacean shells, to aid in cell retention and survival. Ravi Bellamkonda’s lab at Georgia Tech contributed to the paper.

More refinement of these approaches are necessary before clinical use,  but it illustrates how engineered mixtures of progenitor cells and supportive materials are becoming increasingly sophisticated and complicated.

The chitosan gel resembles the alginate material used to encapsulate cells by the Taylor lab. Yoon’s team was testing efficacy in a hindlimb ischemia model, in which a mouse’s leg is deprived of blood. This situation is analogous to peripheral artery disease, and the readout of success is the ability of experimental treatments to regrow capillaries in the damaged leg.

The current paper builds a bridge between the nurse and building block approaches, because the researchers mix two complementary types of cells: an angiogenic one derived from bone marrow cells that expands existing blood vessels, and a vasculogenic one derived from embryonic stem cells that drives formation of new blood vessels. Note: embryonic stem cells were of mouse origin, not human. Read more

Posted on by Quinn Eastman in Heart Leave a comment

There will be microparticles (in stored blood)

More than 9 million people donate blood in the United States every year, according to the American Red Cross. Current guidelines say that blood can be stored for up to six weeks before use.

What happens to red blood cells while they are in storage, which transfusion experts call the “storage lesion”? Multiple studies have shown that older blood may have sub-optimal benefits for patients receiving a transfusion. The reasons include: depletion of the messenger molecule nitric oxide, lysis of red blood cells and alterations in the remaining cells’ stiffness.

To that list, we could add the accumulation of microparticles, tiny membrane-clothed bags that contain proteins and RNA, which have effects on blood vessels and the immune system upon transfusion. Note: microparticles are similar to exosomes but larger – the dividing line for size is about 100 nanometers. Both are much smaller than red blood cells.

EUH blood bank director John Roback recently gave a talk on the blood storage issue, and afterwards, cardiologist Charles Searles and research fellow Adam Mitchell were discussing their work on microparticles that come from red blood cells (RBCs). They have been examining the effects RBC-derived microparticles have on endothelial cells, which line blood vessels, and on immune cells’ stickiness.Red blood cell microparticles280

Mitchell mentioned that he had some striking electron microscope images of microparticles and some of the particles looked like worms. With the aim of maintaining Lab Land’s “Cool Image” feature, I resolved to obtain a few of his photos, and Mitchell generously provided several.

“Those worms definitely had me mesmerized for a while,” he says.

In his talk, Roback described some of the metabolomics research he has been pursuing with Dean Jones. Instead of focusing only on how long blood should be stored, Roback’s team is examining how much differences between donors may affect donated blood’s capacity to retain its freshness. Read more

Posted on by Quinn Eastman in Heart, Immunology Leave a comment