Not just cholesterol
Scientists have found a link between some gene variants and atherosclerosis
Anna Yudina, "Scientific Russia"
Cholesterol-independent gene variants increase the risk of heart disease, diabetes, high blood pressure, according to a press release Scientists find genetic link to clogged arteries.
Article by Jung et al. SVEP1 is a human coronary artery disease locus that promotes atherosclerosis published in the journal Science Translational Medicine – VM.
High cholesterol is the most commonly understood cause of atherosclerosis, hardening of the arteries, which increases the risk of heart attack and stroke. But now scientists from Washington University School of Medicine in St. Louis have identified a gene, one of the variants of which probably plays a causal role in coronary artery disease, regardless of cholesterol levels. The gene may also play a role in the development of cardiovascular diseases such as high blood pressure and diabetes.
By studying mice and human genetic data, the researchers found that a variant of the SVEP1 gene produces a protein that stimulates plaque formation in the arteries. Mice that lacked one copy of SVEP1 had fewer plaques in their arteries than mice with both copies. The researchers also selectively reduced protein in the artery walls of mice, which further reduced the risk of atherosclerosis.
By evaluating a person's genetic data, the researchers found that genetic variations affecting the levels of this protein in the body correlate with the risk of plaque in the arteries. Genetically determined high protein levels mean a higher risk of plaque development and vice versa. Similarly, they found that higher protein levels correlated with a higher risk of diabetes and higher blood pressure readings.
"Cardiovascular diseases remain the most common cause of death worldwide," he said Cardiologist Nathan O. Stitziel, MD, Associate Professor of Medicine and Genetics. – The main goal of the treatment of cardiovascular diseases is properly focused on lowering cholesterol levels. But there must be causes of cardiovascular diseases that are not related to cholesterol - or lipids – in the blood. We can reduce cholesterol levels to very low levels, but some people will still carry a residual risk of developing coronary heart disease in the future. We're trying to figure out what else is going on so we can improve on that as well."
This is not the first identified non-lipid gene that is involved in cardiovascular diseases. But the exciting aspect of this discovery is that, according to the researchers, it is better suited for developing future treatments.
Researchers, including co-authors In-Hyuk Jung, Ph.D., full-time researcher, and Jared S. Elenbaas, a doctoral student in Stiziel's lab, also showed that this protein is a complex structural molecule and is produced by smooth vessels. Muscle cells, which are cells of the walls of blood vessels, contract and relax the vascular network. The protein has been shown to cause inflammation in plaques on artery walls and make plaques less stable. Unstable plaques are especially dangerous because they can come off, leading to the formation of a blood clot that can cause a heart attack or stroke.
"In animal models, we found that the protein induces atherosclerosis and contributes to plaque instability," Jung said. "We also saw that it increases the number of inflammatory immune cells in plaques and reduces collagen, which performs a stabilizing function in plaques."
According to Stiziel, other genes previously identified as increasing the risk of cardiovascular disease, regardless of cholesterol, appear to play a widespread role in the body and, therefore, are more likely to have far-reaching undesirable side effects if they are blocked in order to prevent cardiovascular disease. Although SVEP1 is necessary for early embryo development, according to the researchers, eliminating the protein in adult mice did not have a harmful effect.
"Human genetic data has shown that this protein occurs naturally in a wide range in the general population, which suggests that we could change its levels in a safe way and potentially reduce the risk of coronary heart disease," said Elenbaas.
Current work in Stiziel's group is focused on finding ways to block the protein or reduce its levels in an attempt to identify new compounds or possible treatments for coronary heart disease and possibly high blood pressure and diabetes. The researchers worked with the University of Washington's Office of Technology Management (OTM) to file a patent for a therapy targeting the SVEP1 protein.
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