Heart disease tends not to be disclosed until decades after its onset. As you get older, your heart and blood vessels change, and risk factors such as diet and genetics can cause plaque to build up in your arteries, making it difficult to pump blood around your body, including the heart itself. As the oxygen supply for fuel decreases, the heart gradually weakens.

Heart disease has been the leading cause of death in the United States since 1950, accounting for about one in five deaths, despite advances in treatments for the condition, such as statin drugs to reduce plaque buildup. is occupying. Because heart disease begins long before symptoms appear, Dr. John Conhilas, The professor of physiology and member of the Sarver Heart Center believes scientists need to take a big step back and pinpoint where things are starting to go wrong.

“There are many paths to heart disease,” says Dr. Konhilas. “Can you identify and name all the different streets leading to it?”

Dr. Konhilas is co-director of the Cardiovascular and Pulmonary Interdisciplinary Training (CVP) research program. The program has been funded by the National Institutes of Health since 1969 and for nearly the entire history of the university. Dr. Konhilas points to the Romanowski Institute as an example of a CVP research team that is taking a step back to investigate where the road to heart disease begins.

“If we can better understand heart disease at the cellular and molecular level, we can promote healthy arterial architecture.” Dr. Casey Romanoski, Associate Professor of Cellular and Molecular Medicine. Her lab studies the endothelial cells that line the edges of arteries in a single layer. “These cells are sensors that sense what’s going on in the blood.”

Anna Golebiwski A PhD student in molecular medicine, he studies how these cells “sense” their surroundings, how they respond to microenvironmental triggers, and what role they play in heart disease. I would like to know exactly what it is doing. And she believes the answers are found not by following a straight line, but by following a curve.

Blood vessels throw curveballs

When blood passes through curves and hairpin bends in the upper part of the heart, such as the aortic arch, it creates a turbulent blood flow pattern in the endothelium. Professor Golebiwski said these cells could sense changes in force and respond by releasing inflammatory signals, causing a feedback loop where chronic inflammation attracts plaque, which itself increases the amount of inflammation. states that it is possible.

“Chronic inflammatory conditions make the area more susceptible to plaque development. Inflammatory signals recruit immune cells to remove deposits, but too much inflammatory signaling can cause plaques to become necrotic. and can become unstable,” Dr. Golebiwski said. “Plaque builds up where blood vessels have bends. It’s not the curvature itself that causes plaque buildup, but something about the flow pattern created by the curvature makes that area more susceptible to plaque buildup.” It makes some people more sensitive than others.”

To investigate why some people react differently to blood rapidly spinning through blood vessels, Golebiewski created a petri dish in which healthy endothelial cells were arranged in a single layer on top of which liquid was rotated. We recreated the blood flow inside.

“We use that device to mimic two patterns of blood flow: turbulent blood flow through curved lines and uniform blood flow through straight sections,” she said. “The same amount of shear stress is applied. I’m looking at how genes are expressed within these cells in response to these patterns.”

The cells came from about 150 organ donors in the Los Angeles area, most of whom died in car or motorcycle accidents. Small samples were stored before being transplanted into recipients, giving researchers access to genetically diverse heart cells.

“We don’t know who they are. Everything we learn about them can be learned from their DNA and genetic level,” Dr. Romanoski said. “Their cells respond differently to the inflammatory conditions we put them in.”

Although these cells resulted from tragedy, they may one day help researchers learn more about how heart disease affects people around the world.

“The more genetically diverse a population is, the more tests we can run and the more we can learn,” Golebiewski said. “So much genetic research has been done primarily on people of European ancestry. It’s really exciting to be able to work with a more diverse population.”

Developing the next generation of researchers

Since 1969, Tucson School of Medicine has trained approximately 300 scientists through the CVP program. More than 90% go on to research careers and dedicate their lives to solving cardiovascular mysteries. Dr. Konhilas says he is particularly proud of the rapid increase in productivity seen over the past decade.

“We have doubled the number of publications and the number of grants in the last five years compared to the last 10 years,” he said. “These types of funding mechanisms don’t exist without institutional support. This was essential to winning this grant over and over again.”

In recent years, Dr. Conhilas says, they have expanded trainees’ access to key resources, improved health insurance options, included them in important conferences, and guided them through the grant application process. These benefits are a boost for Golebiewski, who recently received a prestigious grant from the American Heart Association and plans to become an AHA fellow after completing his current research.

Golebiewski also says he has grown greatly under Dr. Romanowski’s guidance.

“I’ve been incredibly lucky to have mentors who support my professional and personal goals and make sure I have everything I need to succeed,” she says. said.

“Anna has a bright future ahead of her, and I feel very fortunate to have her join my lab,” added Dr. Romanoski. “Research can be time-consuming. It’s a marathon, not a sprint. Mentoring gives me satisfaction. I have far more control over mentoring than I do over how cells behave.” It’s really important to me to pass that on to the next generation.”

piecing together the puzzle

For most of us, we hope that the specialized science performed in the laboratory will one day help us and our loved ones. Although her lab does not develop drugs, Dr. Romanoski shares that dream.

“Endothelial cells are present in all of our tissues and play an important role in diabetes and obesity,” Dr. Romanoski said. “We hope that the research we are undertaking will have a far-reaching impact beyond heart disease.”

The Romanowski Institute’s research into how blood affects cells as it travels through the body’s 60,000 miles of blood vessels may one day help in the search for better medicines, but for now they are focuses on elucidating the internal structure of the circulatory system. Building these foundations now will give future scientists a starting point for new research into prevention, treatment, and cures.

“There is great potential in trying to understand how the body works at the cellular level, because we have yet to discover how it works. Because there isn’t,” said Dr. Romanoski, who is also a member of the Sarver Heart Center. BIO5 Institute. “Basic research is about collaborating, building knowledge, and doing experiments that no one else in the world has ever done. We might find genes that aren’t there and are just lurking in the shadows. We don’t even know what we’re going to find. That’s really exciting.”

Dr. Conhilas expressed a similar opinion.

“We need to understand diseases before we get sick. Ultimately, understanding how things work at a fundamental level will lead to some remarkable clinical results.” “You will be able to do it,” he said. “I hope there are big discoveries, and students need to work on the fundamental level of how things work. It always comes back to physiology.”

Golebiski says that despite how complex heart disease is, seeing just one piece of the puzzle brings great satisfaction.

“There are so many facets to this disease. We are analyzing this and looking at one aspect: the forces from the bloodstream on endothelial cells,” she said. “The most rewarding thing about looking at all the data is knowing that I have accomplished so much. I haven’t reached any major conclusions yet, but my efforts so far are definitely paying off. Masu.”