Researchers at the UVA School of Medicine have identified a gene that plays a crucial role in determining the risk for heart attacks, deadly aneurysms, coronary artery disease and other dangerous vascular conditions.
The discovery advances the human understanding of the underlying causes of serious health conditions such as atherosclerosis (hardening of the arteries), and moves humans closer to finding new treatments and preventative measures to help individuals living longer, healthier lives.
“The first step toward 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,” principal investigator Dr. Clint L. Miller of UVA’s Center for Public Health Genomics and Departments of Biochemistry and Molecular Genetics and Public Health Sciences said. “By gaining insight into the gene regulatory networks that underlie specific vascular disease pathways, we can develop more tailored interventions or risk metrics for patients.”
Miller and his team’s new discovery identifies a gene that directs an entire network of genes and processes. FHL5 acts like a military general who deploys troops on the battlefield. Miller and his team evaluated FHL5’s effect on smooth muscle cells, the cells that form the structure for arteries, to understand how the FHL5 encoded protein functions. They found that FHL5 was too active. The cells began to accumulate too much calcium, which 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. The excess gene activity also contributed to other critical cellular activities related to vascular disease.
FHL5’s role does not stop there. The scientists found that 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.
“By mapping the downstream effectors of vascular remodeling, we hope to shed light on preventative mechanisms,” Miller said. “Unbiased genetic studies led us to this specific cofactor. However, studying its regulatory network could explain its link to several vascular diseases.”
The UVA team’s findings are published in the scientific journal Circulation Research.
“We hope this work serves as template for future studies to investigate the functional consequences of perturbing key regulators in the vessel wall,” 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.”