American Heart Association Merit Award fuels three research avenues to tackle heart disease

A physician-scientist from Massachusetts researching whether chemicals naturally occurring in foods could help treat heart disease, a genetics expert from Pennsylvania exploring the molecular mechanisms of lipid metabolism and cardiovascular diseases and a California-based professor of cardiovascular medicine studying how vaping impacts the development of abdominal aortic aneurysms are the most recent American Heart Association Merit Award recipients. Over the next five years, each researcher will receive a total of $1 million in funding from the Association, the world's leading voluntary organization focused on heart and brain health and research, now celebrating 100 years of lifesaving work.

The American Heart Association's Merit Award is one of the highest honors given by the Association. The Merit Award supports highly promising, novel research that has the potential to move cardiovascular science forward quickly, with high impact. The recipient of the 2024 award are:

• Joseph Loscalzo, M.D., Ph.D., FAHA, the Distinguished Hersey Professor of the Theory and Practice of Medicine and the Samuel A. Levine Professor of Medicine at Harvard Medical School, former chair of the department of medicine and physician-in-chief emeritus at Brigham and Women's Hospital in Boston;
• Daniel J. Rader, M.D., FAHA, Seymour Gray Professor of Molecular Medicine, chair of the Department of Genetics at the Perelman School of Medicine at the University of Pennsylvania School of Medicine and chief of the Divisions of Human Genetics at Penn Medicine and the Children's Hospital of Philadelphia; and
• Philip S. Tsao, Ph.D., FAHA, a professor of medicine in cardiovascular medicine at Stanford University School of Medicine and associate chief of staff for precision health at the VA Palo Alto Health Care System in Palo Alto, California.

This award supports exceptional scientists with established track records of success. These are true innovators who propose novel approaches to major research challenges in the areas of heart disease, stroke and brain health. Specifically, their research has the potential to produce unusually high impact toward the American Heart Association's mission to be a relentless force for a world of longer, healthier lives. As a recipient of this award in 2017, I know it comes with great honor and, also, great responsibility. This year's recipients are already recognized leaders in the field of cardiovascular research, and I know they will meet the next challenges before them as champions of transformative science in our fight against heart disease and stroke."

Joseph C. Wu, M.D. Ph.D., FAHA, American Heart Association volunteer president, director of the Stanford Cardiovascular Institute and Simon H. Stertzer Professor of Medicine and Radiology at Stanford School of Medicine

Loscalzo's research will focus on the link between heart disease and certain foods, or chemicals naturally contained in foods. Using high-speed computers and model systems, he plans to explore many of the 135,000 'natural' chemicals that have been identified in the world's food supply. His research will focus on how these food chemicals interact with proteins in cells to affect how the cell works and, ultimately, which chemicals may protect the heart. Using this information, his team will then investigate ways to use these compounds to create diets that specifically protect against heart disease and lay the groundwork for developing new drugs that can be used for heart disease treatment.

"One might ask what makes this project exciting and worth funding? Many scientists and doctors have worked hard to create diets that are good for your heart in the past. Their work has been based on only a small amount of information about the composition of food, less than 1%. Our approach is much larger in scope," Loscalzo said. "We will use modern technologies to explore the great number of chemicals in the food supply. We will then be able to identify among them new 'natural' therapies for heart disease for the health of all people."

Rader's research will focus on new genes and pathways altering lipid metabolism and causing cardiovascular disease revealed through large-scale human genetics. Blood lipids such as cholesterol and triglycerides are causal risk factors for coronary heart disease as well as several other types of cardiovascular disease, such as aortic stenosis). Genetics play a major role in lipid metabolism and cardiovascular disease and many new genes have been identified for which the underlying biology is not understood. Using computational, experimental and human-based studies, Rader will focus on new genes expressed in the liver that modulate both blood lipids and cardiovascular diseases to better understand the molecular mechanisms and determine the potential for new therapeutic approaches.

"While we know many of the risk factors of heart disease are inherited and have identified hundreds of genes involved, we don't know how most of these genes are affecting the risk of heart disease. We have a huge need to figure out how these genes are working together to promote, or protect, heart disease," Rader said. "By doing studies in model systems and in humans, we will help solve some of these mysteries and hope to better understand how genes influence the development of cardiovascular disease. Unlocking the biological and cellular mechanisms of heart disease can help us identify novel therapeutic targets that can potentially transform into medical advances to improve population health."

Tsao's research will focus on how vaping may impact the risk of developing an abdominal aortic aneurysm (AAA), which is a weakening of the major artery in the abdominal area. Like a bubble on the side of a bicycle tire, pressure within the artery will cause an AAA bubble to continue to grow until it ruptures, often resulting in death. While some genes have been associated with the risk of developing AAA disease, none is thought to cause an AAA by itself. Instead, it is likely a person's lifestyle acts together with genes to drive AAA disease. Smoking is a prevalent risk factor among people who have an abdominal aortic aneurysm.

"Nearly 90% of people with an abdominal aortic aneurysm have a history of tobacco use. In fact, AAA disease is more closely associated with cigarette smoking than any other tobacco-related disease except lung cancer. However, to date, there have been very few studies to explain the relationship between smoking and AAA disease," Tsao said. "We know even less about the effects of vaping on the development of an AAA. Yet, given how popular vaping is, especially with young adults, understanding the effects on AAA disease is very important. We propose to study the ways by which e-cigarette vapor affects specific genes to worsen AAA growth. By identifying these mechanisms, we hope to discover new ways to treat abdominal aortic aneurysms. Since smoking is related to many diseases, these studies may also help us understand the more broad, long-term health effects of e-cigarettes and vaping."

Funding scientific research and discovery through initiatives like the annual merit awards is a cornerstone of the century-old American Heart Association's lifesaving mission. The Association has now funded more than $5.7 billion in cardiovascular, cerebrovascular and brain health research since 1949, making it the single largest non-government supporter of heart and brain health research in the U.S. New knowledge resulting from this funding continues to save lives and directly impact millions of people in every corner of the U.S. and around the world.