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Sunday, May 28, 2023

UVA Discovers Gene That Shapes Risk for 

Heart Attacks and Vascular Diseases

The University of Virginia School of Medicine (UVA) announced this week their research has identified a gene that plays a crucial role in determining our risk for heart attacks, deadly aneurysms, coronary artery disease and other dangerous vascular conditions, all illnesses that disproportionately affect Black patients.

According to the American Heart Association, Black patients in the United States have a higher prevalence of heart disease compared to other racial and ethnic groups. Specifically, it says Black patients are more likely to have high blood pressure, diabetes, and obesity, which are all risk factors for heart disease.

This discovery “advances our understanding of the underlying causes of a wide range of serious health conditions, including atherosclerosis (hardening of the arteries), and moves us closer to new treatments and preventive measures that could help people live longer, healthier lives,” says Dr. Clint L. Miller, PhD, UVA’s principal investigator for the research project.

Dr. Miller points to lifestyle choices such as smoking, sedentary behavior, and a diet heavy in red meat as playing major roles in the development of vascular diseases such as coronary artery disease, a leading cause of death worldwide. 

“But our genes, the genetic material we inherit from our parents, also shape our risk. Understanding precisely how, however, has been a major challenge for scientists.” says Dr. Miller. “By identifying these early-stage risk factors we hope to raise awareness for more proactive monitoring of coronary calcium and elevated blood pressure, which can help reduce or eliminate heart health disparities.”

“The first step towards translating the knowledge of population risk for vascular disease is disentangling the fundamental cellular processes that could be affected. Ideally this can be done systematically in disease-relevant models,” said Dr. Miller, who holds a PhD, in pharmacology. “By gaining insight into the gene regulatory networks that underlie specific vascular disease pathways, we can develop more tailored interventions for patients.”

Given the high rates of heart disease in the Black community this discovery holds great promise for many African Americans. This writer believes any pharmaceutical interventions developed as a result of these discoveries should include Black people in the clinical trials to help ensure its effectiveness for all patients. 

Ethical, well-regulated clinical trials are an essential tool in eliminating health disparities. In order to properly administer and access its effectiveness, when a new drug enters the market researchers will need to seek participants beyond the historically narrow and homogeneous demographic population of white males.

“We are involved in studies to identify African ancestry specific genetic risk factors for heart disease and hope this work will inform follow up clinical trials to develop more effective and tailored interventions,” said Dr. Miller. 

  The subtle changes that take place in our blood vessels over time are extremely complex. In coronary artery disease, for example, scientists have determined that genes that affect our risk can be found at more than 300 locations on our chromosomes. That’s a vast area for scientists to explore.

 The new discovery from Dr. Miller and his collaborators, however, identifies a gene that directs an entire network of genes and processes. In that sense, the gene, FHL5, is like a general deploying troops on the battlefield. That makes it an extremely attractive molecule for scientists seeking to unravel the targetable pathways for new treatments or prognostic tools.

 To understand how the FHL5 encoded protein functions, Dr. Miller and his team evaluated its effect on smooth muscle cells, the cells that form the structure of our arteries. They found that when FHL5 was too active, the cells began to calcify – accumulating too much calcium. This is a key step in atherosclerosis, the buildup of harmful plaque in the arteries that can lead to heart attacks, strokes and other serious health problems.

 ButFHL5’s role doesn’t stop there. Instead, the scientists found, it has a far-reaching effect on other genes and cellular processes that shape the “remodeling” that occurs in our arteries over time, the researchers report in a new scientific paper. “Unbiased genetic studies led us to this specific cofactor. However, studying its regulatory network could explain its link to several vascular diseases,” said Dr. Miller.

He adds, “The identification of this key regulator gives scientists important new insights into the genetic factors that contribute to vascular disease and provides an attractive and influential target as they develop new treatments and work to prevent the harmful changes that causes those diseases.”

“We hope this work serves as a template for future studies to investigate the functional consequences of perturbing key regulators in the vessel wall,” Dr. Miller said. “Translating this knowledge to the clinic will require ongoing interdisciplinary collaborations, and we look forward to ultimately seeing the impact of these genetic studies.”  

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