- Plasminogen activator inhibitor-1, or PAI-1, is a naturally occurring protein in the blood vessels that promotes cell migration.
- It over-accumulates in the arteries and causes block formation in conditions like diabetes and obesity.
- New drug, PAI-039 inhibited cell migration due to PAI-1 and prevented block formation in the arteries.
A new therapeutic approach to prevent heart attacks, stroke and other diseases caused by blocked blood vessels has been developed.
A recent study by researchers at the University of Missouri School of Medicine has shown that a protein inhibitor drug prevents these blockages.
According to the American Heart Association, approximately 2,200 Americans die each day from heart attacks, strokes and other cardiovascular diseases.
"Arteries are living hoses that narrow and enlarge in order to regulate blood flow to organs and muscles," said William Fay, M.D., the J.W. and Lois Winifred Stafford Distinguished Chair in Diabetes and Cardiovascular Research at the MU School of Medicine and senior author of the study.
"Smooth muscle cells in the artery regulate blood flow by constricting and relaxing. However, when chronic inflammation occurs in a blood vessel - typically in response to diabetes, high cholesterol and cigarette smoking - the smooth muscle cells in the walls of arteries change their behavior. They gradually accumulate inside the artery and narrow the blood vessel. In the case of coronary arteries, which supply blood to heart muscle cells, this process produces blockages that can lead to a heart attack." William added.
Plasminogen activator inhibitor-1, or PAI-1, is a naturally occurring protein within blood vessels that controls cell migration.
There is an over-accumulates of PAI-1 in blood vessels in conditions like diabetes and obesity This promotes block formation not only in arteries but also in vein grafts among patients who have undergone coronary artery bypass graft surgery.
An investigational drug, PAI-039, also known as tiplaxtinin, which was not yet used to treat humans, was tested in mice.
The researchers found that PAI-039 inhibited cell migration of cultured human coronary artery smooth muscle cells, which helped to prevent the development of blockages in arteries and bypass grafts.
"We found that PAI-039 decreased blockage formation by about 50 percent, which is a powerful effect in the models we used," said Fay.
PAI-039 also produced a blood thinning effect that prevents the blood clots which trigger most heart attacks and strokes. In future, PAI-039 or similar drugs could be used to prevent blockages in arteries and bypass grafts.
The study is published inl Arteriosclerosis, Thrombosis, and Vascular Biology, a journal of the American Heart Association.
- William P.Fay et al. Pharmacological Targeting of Plasminogen Activator Inhibitor-1 Decreases Vascular Smooth Muscle Cell Migration and Neointima Formation. Arteriosclerosis, Thrombosis, and Vascular Biology; (2016) doi.org/10.1161/ATVBAHA.116.308344