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

John Calvert

Regrowing adult heart muscle

In adulthood, our hearts generally can’t grow again in response to injury. Emory cardiology researchers Ahsan Husain and Nawazish Naqvi and their colleagues have been chipping away at this biological edifice in animal models, demonstrating that it is possible to remove constraints that prevent the heart from growing new muscle cells.

Husain and Naqvi’s teams accomplished this by combining the thyroid hormone T3 — already FDA approved — with siRNA-based inhibition of an enzyme called DUSP5. Their latest paper, published in the journal Theranostics, applies the combination in an animal model of drug-induced heart failure.

The anticancer drug doxorubicin is sometimes known as the “red devil”

The anticancer drug doxorubicin is notorious for its cardiotoxicity, yet it is a mainstay of treatment for breast cancer in adults and several types of cancer in children. Cardiotoxicity affects a fraction of breast cancer patients treated with doxorubicin (20 percent in some studies) and severely impacts mortality and quality of life.

In the mouse model, doxorubicin generates severe heart failure, with a 40 percent drop in left ventricular ejection fraction (LVEF), a measure of the heart’s pumping capacity. In response to the combination of T3 and DUSP5 siRNA, a large increase in LVEF is seen. The researchers also report that the treatment has a marked effect on the health of the animals, restoring their activity levels, grooming and posture. See the video for an example of a mouse heart treated with the T3/DUSP5 siRNA combination.

The results are potentially applicable to other situations when doctors would want to regrow or repair cardiac muscle. Husain reports plans for a clinical study in patients with drug-induced or other forms of heart failure, supported by a generous gift from the Atlanta-based ten Broeke Family Foundation.

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

Nitrite: from cured meat to protected heart

Nitrite may be best known as a food additive used in cured meats such as hot dogs, but medical researchers are studying how it could treat several conditions, including preventing damage to the heart after a heart attack.

Leaders in the nitrite field are meeting May 11 -13, 2011 at Emory Conference Center in Atlanta. One of the lead organizers is David Lefer, PhD, professor of surgery at Emory University School of Medicine and director of the Cardiothoracic Research Laboratory. Lefer discusses the beneficial effects of nitrite in the video below. More information about the meeting is available here.

Scientists think supplying a pulse of nitrite can reduce injury to heart tissue coming from the interruption of blood flow. Several clinical trials are now investigating nitrite as a therapy for conditions such as heart attack, ruptured aneurysm, sickle cell pain crisis and cardiac arrest.

Nitrite acts as the body’s reserve for nitric oxide, which turns on chemical pathways that relax blood vessels. Delivering nitric oxide directly into the body is expensive and hard to control. Unlike nitric oxide, whose lifetime in the body is a few seconds, nitrite is stable and stored in the body’s tissues and can be delivered in a variety of ways. It is converted into nitric oxide under conditions when the body needs it: lack of blood or oxygen. In addition, sodium nitrite has been used as part of a cyanide antidote kit. This means that safety data on large doses of nitrite in critically ill people is available.

In a 2005 paper published in the Journal of Clinical Investigation, Lefer and colleagues showed that nitrite can reduce damage to the hearts of mice after a simulated heart attack. More recently, assistant professor John Calvert and Lefer have shown that internally generated and stored nitrite is an important way that exercise protects the heart from a heart attack.

Some blood pressure studies underway in Europe have participants consume large amounts of beet juice as their source of nitrate, which is then converted to nitrite in the body.

A wave of public concern about nitrite and its relative nitrate in the 1970s focused on their presence in cured meats and their ability to form nitrosamines, which can be carcinogenic. Subsequent investigation showed that actually, most of the nitrite and nitrate in the average adult’s diet come from vegetables such as broccoli and spinach, and that antioxidants such as vitamin C can prevent nitrosamine formation.

Nathan Bryan, a speaker at the conference from UT-Houston, was featured in a recent television news story about herbal supplements designed to boost nitrite in the body.

Posted on by Quinn Eastman in Heart 2 Comments