Researchers at the School of Medicine have discovered that the answer to cardiovascular disease lies in the cellular “glue” our bodies create to protect us from heart attacks and strokes.

Scientists at the School of Medicine have found an important answer: stroke, heart attack and cardiovascular disease By investigating the biological glues our bodies produce to protect us from deadly dangers.

Researchers led by Dr. Mette Sibelek wanted to better understand the factors that influence the risk of cardiovascular diseases such as atherosclerosis and arteriosclerosis. Atherosclerosis is characterized by the accumulation of fatty plaques within blood vessels. When these plaques form, our bodies build a fibrous cap over them to prevent them from sloughing off and causing heart attacks and strokes.

Sibelek and his team believe that the scaffolding our bodies build on top of these plaques contains important clues that could improve our understanding of cardiovascular disease, the leading cause of death around the world. I thought there might be one. And by taking a smart approach, scientists have gained important new insights that could advance the development of life-saving treatments.

“We have combined 20 years of discoveries in human genetics with the unique resource of smooth muscle cells, a critical component of arteries where plaques develop,” said UVA Center for Public Health Genomics and Department of Biomedical Engineering. Civelek said. “We discovered that our genetic makeup influences how smooth muscle cells secrete proteins that give plaques strength and prevent heart attacks and strokes caused by plaque rupture.”

vital cellular glue

To build a protective scaffold over the potentially deadly plaque, the smooth muscle cells lining blood vessels rely on what is known as the “extracellular matrix,” a protein-rich fibrous glue-like secretes substances. Sibelek and his team measured these and related proteins in smooth muscle cells from 123 heart transplant donors. Scientists were then essentially able to work backwards to identify the genes that make those proteins.

This allowed the scientists to identify 20 locations on the chromosome where genes that affect the production of important proteins are located. They were also able to pinpoint naturally occurring genetic mutations that put certain people at increased risk of atherosclerosis, and identify the types of proteins that contribute to cardiovascular risk. UVA researchers say the new insights could help doctors identify patients who are most at risk of having plaque sloughed off, causing a heart attack or stroke.

The findings also shed important light on why the actions of smooth muscle cells can be beneficial or detrimental in some cases. That information will be a huge asset to researchers trying to develop new treatments for atherosclerosis and cardiovascular disease, Sibelek said.

“We have identified one protein, LTBP1, that appears to play an important role in plaque stability,” he said. “We continue to study whether this protein could be a useful therapeutic target and hope to soon translate our findings into patient care.”

Publication of survey results

The researchers published their findings in the scientific journal Arteriosclelarosis, Throbosis, and Vascular Biology. The research team consists of Dillon Lue, Alicia Beele, Tiit Ord, Minna U. Kaikkonen, Zouhair Aherrahrou, Qi Cheng, Saikat Ghosh, Santosh Karnewar, Vaishnavi Karnewar, Aloke Finn, Gary K. Owens, Michael Joner, Manuel Mayr, and Civelek. it was done. The researchers have no financial interest in this study.

This research was supported by American Heart Association Postdoctoral Fellowship 18POST33990046. University of Eastern Finland. German Cardiovascular Research Center. Corona Foundation, grant S0199/10097/2023. Transformational Project Award 19TPA34910021; National Institutes of Health, Grant R21HL135230 and. R01 HL155165; Academy of Finland, grants 333021 and 335973. European Research Council Horizon 2020 Research and Innovation Program, grant 802825. Finnish Cardiovascular Research Foundation. Sigrid Juselius Foundation. Foundation Leducq, International Network of Excellence Awards 12CVD02, 18CVD02, and 22CVD04, and its Junior Researcher Award.

UVA’s Department of Biomedical Engineering is a joint program between the School of Medicine and the School of Engineering.

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