Genetic Therapy Might Be a Good Approach for Coronary Artery Disease

An international team of scientists, including a researcher from the University of Virginia, has made a significant breakthrough in understanding the genetic factors contributing to calcium buildup in coronary arteries, a condition that can lead to life-threatening coronary artery disease, responsible for a staggering one in four deaths in the United States.

The researchers believe that targeting these newly identified genes with existing medications or nutritional supplements could potentially slow down or even halt the progression of this deadly disease. The study, published in the journal Nature Genetics, focused on coronary artery calcification, a process where calcium accumulates within the walls of coronary arteries.

Even before individuals develop clinical atherosclerotic coronary artery disease, non-invasive computed tomography scans can detect this calcium buildup. This accumulation is a reliable predictor of future cardiovascular events, such as heart attacks or strokes, which are leading causes of death globally. Moreover, coronary artery calcification has been linked to other age-related diseases, including dementia, cancer, chronic kidney disease, and hip fractures. 

Although genetics has long been known to play a role in coronary calcium buildup, only a limited number of contributing genes have been identified. To address this knowledge gap, the researchers conducted a large-scale meta-analysis, pooling data from over 35,000 individuals of European and African ancestry from around the world.

This extensive genetic analysis identified more than 40 candidate genes at 11 different locations on chromosomes associated with coronary artery calcification. Remarkably, eight of these locations had not been previously linked to coronary calcification at all, and five had not been reported in relation to coronary artery disease. These genes are known to play crucial roles in bone mineral content and metabolic pathways involved in the formation of calcium deposits. 

One of the identified genes, ENPP1, is known to be altered in rare cases of arterial calcification in infants. Additionally, genes in the adenosine signaling pathway, which has a role in suppressing arterial calcification, were also found to be involved. 

To validate their findings, the scientists conducted further investigations using human coronary artery tissues and smooth muscle cells. These experiments confirmed the direct impact of these genes on calcification and related cellular processes. 

The implications of these discoveries are profound. With a better understanding of how these genes contribute to coronary artery calcification, researchers can now work towards developing drugs that target these genes or the proteins they encode. Some of these potential treatments may also be influenced by dietary changes or nutrient supplementation, such as vitamins C or D. 

While there is more research to be done to determine the most effective ways to target these genes and affected pathways, the new insights provide hope for improved risk evaluation of patients and early interventions to prevent the progression of coronary artery disease. This could be a game-changer in the fight against a disease responsible for more than 17 million deaths globally each year. 

The lead researcher, Clint L. Miller from the UVA School of Medicine’s Center for Public Health Genomics, emphasized the power of interdisciplinary collaboration in this research. He also expressed optimism about translating these preliminary findings into clinical applications and identifying additional genes that could enhance risk prediction across diverse populations. 

The study has unveiled crucial genetic factors contributing to coronary artery calcification, offering potential avenues for novel treatments and preventive measures against coronary artery disease, a major global health challenge. 

Journal Reference  

Maryam Kavousi et al, Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification, Nature Genetics (2023). DOI: 10.1038/s41588-023-01518-4.