AHA Awarded a Fellowship to Dr. Minzhi Yu to Continue the Quest to Develop a Drug to Stop a Silent Killer
American Heart Association Awarded a Fellowship to Dr. Minzhi Yu to advance her quest for an aneurysm drug.
Every year, an estimated 200,000 older adults in the US are diagnosed with an abdominal aortic aneurysm (AAA). AAA is a balloon-like bulge or widening in the abdominal aorta, the large artery that carries blood from the heart to the lower body, that occurs when the walls of the blood vessel are weakened.
Small, slow-growing aneurysms often cause no symptoms, but when they leak or rupture, they can be deadly. Currently, the treatment options for AAA are limited and risky — limited because there is no drug to slow down the growth of aneurysms and risky because the surgery to repair large or ruptured aneurysms can be difficult, especially in older adults and those with other cardiovascular conditions.
Minzhi Yu, a research fellow at the University of Michigan College of Pharmacy Department of Pharmaceutical Sciences, is working to develop a new drug to treat AAA in addition to surgery. She is testing compounds that show promise for controlling the growth and preventing the rupture of AAAs.
Inflammation is thought to be a significant culprit in AAA. It damages the cells that line the walls of arteries and breaks down the extracellular matrix that glues the blood vessels together. Dr. Yu is developing ways to use a synthetic form of high-density lipoprotein, the so-called “good cholesterol,” to calm that response and help deliver other drugs that also help heal the blood vessel.
“This good cholesterol can be synthesized as sHDL, a nanoparticle that can clean up blood vessels and also help maintain a very healthy blood vessel environment, so they help tamp down inflammation,” Dr. Yu explains.
What’s more, sHDLs can serve as a carrier for other drugs, transporting them to blood vessel walls. One promising candidate is nitro-oleic acid (NO2-OA), a new small-molecule drug that can modify a variety of proteins to reduce inflammation. She is working on combining this compound with sHDLs to carry their combined inflammation-fighting power directly to aneurysms.
One drawback with NO2-OA is that it is not stable in the body for very long, she says. The advantage of combining it with a carrier is that sHDL mimics the naturally occurring blood component closely, so the body is less likely to recognize it as foreign and mount an immune response.
These compounds are still experimental and not yet approved for human use, but they offer a promising approach to improved treatment. Recognizing the potential of her research, the American Heart Association awarded Dr. Yu a two-year postdoctoral fellowship in January 2024 to support her work.
With this support, Dr. Yu is working to find the best and most effective combination of these drugs, assess their combined protective functions on cells, and study their effectiveness in shrinking and stabilizing aneurysms in animal models.
AAA is most common in adults over 50, especially those who smoke or have high blood pressure, high cholesterol, heart disease, or peripheral vascular disease. It’s most common in white males and tends to run in families. Symptoms of a developing or rupturing aneurysm include sudden, severe abdominal or back pain.
In many cases, however, aneurysms are silently lurking and incidentally discovered while scanning for some other condition, says Dr. Yu. “Once it’s spotted, there’s no way to control it. You have to watch and wait and see if it grows to a point where surgery is required. That puts both patients and doctors in a very difficult situation.”
“By combining these two compounds, we hope to develop a drug that will offer an effective treatment to AAA.”
Dr. Yu is just one example of the incredible research that is going on at the College of Pharmacy and the commitment we make to advancing science to improve human health.