Researchers reveal a previously unknown genetic effect that can increase or decrease the risk of heart disease



Atherosclerotic disease, the slow and silent hardening and narrowing of the arteries, is one of the leading causes of mortality worldwide, responsible for more than 15 million deaths each year, including approximately 610,000 people in the United States.

Now, researchers may know one more reason why some people are more likely to develop the disease. In an article published this month in the Procedures of the National Academy of Sciences, a team of physicians, geneticists and biologists, including members of the University of Arizona, describes a previously unknown genetic effect that can increase or reduce the risk of coronary artery disease or ischemic stroke.

"People with the beneficial version of the genetic factor we discovered have fewer or less activated inflammatory cells lining blood vessels," said Casey Romanoski, PhD, assistant professor of cellular and molecular medicine at the University of Arizona School of Medicine in Tucson co-author of the study. "It basically means that they will be more resistant to accumulating plaque in their blood vessels."

In collaboration with researchers at the University of Chicago Medical Center, the team found that a common sequence variant in regulatory DNA, known as rs17114036 and located on chromosome 1p32.2, benefits the vascular endothelium, the cells lining the interior of the blood. vessels

The endothelium helps smooth and accelerate blood flow through complex vascular intersections, where branches or bifurcations interrupt the flow of an artery to two smaller vessels. When the flow is smooth and in one direction, the endothelium is calm; When the flow is altered, there is chronic local inflammation and the formation of atherosclerotic lesions that cause heart attacks and strokes.

The research team discovered that rs17114036 modifies the way in which blood flow patterns affect inflammation, which can change a person's risk of cardiovascular disease. However, only about 5 percent of the population has the protective genetic factor.

These people "have won the genetic lottery," said Yun Fang, PhD, assistant professor of medicine at the University of Chicago and lead author of the study.

For the other 95 percent of the population, things are slightly worse. About 19 out of 20 people, "I carry the risk allele," said Dr. Fang. "It increases the endothelial response to the alteration of blood flow, which increases the risk of cardiovascular disease or stroke."

the PNAS The study shows that a genetic variant can influence important endothelial function and that genetic variants contribute to individual variation, such as susceptibility to coronary artery disease.

For researchers at the University of Chicago, the next step may be the development of nanoparticles or ultra small particles that can replicate the benefits of rs17114036.

"Atherosclerosis occurs where there is an altered (blood) flow," Dr. Fang explained. "If we can make the endothelial cells feel as if they are exposed to a unidirectional flow, there should be less atherosclerosis."

Dr. Romanoski, who specializes in genetics and genomic analysis and is a member of the UA BIO5 Institute, plans to continue linking genetics to various diseases, particularly those related to the heart and lungs.

Source:

https://uahs.arizona.edu/news/ua-researchers-help-discover-genetic-factor-can-help-or-hurt-risk-heart-disease

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