Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

fluid dynamics

Mapping shear stress in coronary arteries can help predict heart attacks

A heart attack is like an earthquake. When a patient is having a heart attack, it’s easy for cardiologists to look at a coronary artery and identify the blockages that are causing trouble. However, predicting exactly where and when a seismic fault will rupture in the future is a scientific challenge – in both geology and cardiology.

In a recent paper in Journal of the American College of Cardiology, Habib Samady, MD, and colleagues at Emory and Georgia Tech show that the goal is achievable, in principle. Calculating and mapping how hard the blood’s flow is tugging on the coronary artery wall – known as “wall shear stress” – could allow cardiologists to predict heart attacks, the results show.

Map of wall shear stress (WSS) in a coronary artery from someone who had a heart attack

“We’ve made a lot of progress on defining and identifying ‘vulnerable plaque’,” says Samady, director of interventional cardiology/cardiac catheterization at Emory University Hospital. “The techniques we’re using are now fast enough that they could help guide clinical decision-making.”

Here’s where the analogy to geography comes in. By vulnerable plaque, Samady means a spot in a coronary artery that is likely to burst and cause a clot nearby, obstructing blood flow. The researchers’ approach, based on fluid dynamics, involves seeing a coronary artery like a meandering river, in which sediment (atherosclerotic plaque) builds up in some places and erodes in others. Samady says it has become possible to condense complicated fluid dynamics calculations, so that what once took months now might take a half hour.

Previous research from Emory showed that high levels of wall shear stress correlate with changes in the physical/imaging characteristics of the plaque over time. It gave hints where bad things might happen, in patients with relatively mild heart disease. In contrast, the current results show that where bad things actually did happen, the shear stress was significantly higher.

“This is the most clinically relevant work we have done,” says Parham Eshtehardi, MD, a cardiovascular research fellow, looking back on the team’s previous research, published in Circulation in 2011.  Read more

Posted on by Quinn Eastman in Heart Leave a comment

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.

Posted on by Quinn Eastman in Heart Leave a comment