Newswise —
Researchers from the University of School of Medicine have discovered a gene that plays a pivotal role in determining our susceptibility to life-threatening vascular conditions such as heart attacks, deadly aneurysms, and coronary artery disease.
This groundbreaking discovery enhances our comprehension of the fundamental causes of numerous severe health issues such as atherosclerosis (artery hardening) and brings us one step closer to developing novel treatments and preventative measures that could prolong and improve people's lives.
According to Clint L. Miller, PhD, the lead researcher from UVA's Center for Public Health Genomics and Departments of Biochemistry and Molecular Genetics and Public Health Sciences, the primary step in applying the knowledge of population risk for vascular disease is to comprehend the essential cellular processes that may be impacted. This process can be methodically carried out in disease-relevant models. "By gaining a deeper understanding of the gene regulatory networks that underlie specific vascular disease pathways, we can create more personalized interventions or risk evaluations for patients," he added.
Genetic Factors in Vascular Disease
Lifestyle choices, such as smoking, sedentary behavior, and a diet high in red meat, are significant factors in the onset of vascular diseases, including coronary artery disease, which is a leading cause of death worldwide. However, our genes, which we inherit from our parents, also influence our susceptibility. Nevertheless, comprehending the precise mechanisms by which genes affect our risk has presented a significant challenge for scientists.
The reason for this challenge is that the gradual alterations that occur in our blood vessels over time are exceedingly intricate. For instance, in the case of coronary artery disease, researchers have identified more than 300 locations on our chromosomes where genes that impact our risk are located. This vast area of exploration presents a significant hurdle for scientists to investigate thoroughly.
Nonetheless, the recent breakthrough made by Miller and his team is that they have discovered a gene, FHL5, which governs an entire network of genes and processes. In this way, FHL5 acts as a commander directing troops on the battlefield, and as such, it presents an immensely promising molecule for researchers seeking to unravel the modifiable pathways for new treatments or prognostic tools.
Miller and his team investigated the mechanism of action of the FHL5 encoded protein by analyzing its impact on smooth muscle cells, which form the structure of our arteries. They discovered that when FHL5 was overly active, these cells began to calcify, resulting in an excessive accumulation of calcium. This process is a crucial step in atherosclerosis, which is the harmful buildup of plaque in the arteries that can cause heart attacks, strokes, and other severe health issues. Additionally, the increased gene activity influenced other essential cellular activities related to vascular disease.
However, FHL5's significance extends beyond its role in calcium accumulation. The researchers discovered that it has a far-reaching influence on other genes and cellular processes that contribute to the "remodeling" that happens in our arteries over time, as per their recent scientific publication. "Through identifying the downstream effectors of vascular remodeling, we aspire to discover preventative mechanisms," Miller stated. "Unbiased genetic studies led us to this particular cofactor. However, delving into its regulatory network may clarify its association with various vascular diseases."
The discovery of this critical regulator provides scientists with crucial new information about the genetic factors that contribute to vascular diseases. It also presents a promising and potent target as they work towards developing novel treatments and preventing the harmful alterations that cause such conditions.
Miller expressed hope that this research serves as a model for forthcoming studies to explore the functional ramifications of altering key regulators in the vessel wall. He also mentioned that translating this knowledge into clinical practice will necessitate ongoing interdisciplinary collaborations, and he looks forward to witnessing the impact of these genetic studies in the future.
Findings Published
The researchers' findings have been published in the scientific journal Circulation Research. The team, comprising of numerous researchers, including Doris Wong, Gaëlle Auguste, Christian L. Lino Cardenas, Adam W. Turner, and many others, collaborated on this research. Miller, the principal investigator, has no financial interest in the study, and a complete list of the authors' disclosures is included in the paper. The researchers' findings offer crucial insights into the genetic factors contributing to vascular diseases, paving the way for the development of new treatments and preventive measures.
The research was supported by the National Institutes of Health, grants R01HL148239, R01HL164577, R00HL125912, F31 HL156463, R01HL142809 and K01HL164687; and the Fondation Leducq, ‘PlaqOmics’ 18CVD02.
To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.
RSS