Cell-type-specific insights into the function of risk factors for coronary artery disease

Using single-cell technology, new research highlights the importance of genetic risk factors for the development of coronary artery disease and the diversity of cells involved. The researchers analyzed lesions of human atherosclerosis to map the chromatin accessibility of more than 7,000 cells. Chromatin accessibility is known to reflect active regions and genes within the genome.Survey results published in Circular research..

Genome-wide association studies of the human genome have identified more than 200 loci associated with coronary artery disease. Over 90% of them are located outside the protein-encoding gene, the so-called cis-regulatory element, and their importance in the pathogenesis of coronary artery disease remains unclear.

Previous studies have shown that a variety of factors are involved in the development of coronary artery disease. cell And its subtypes. The currently published study is the first to use single-cell technology to map epigenetic changes in these cells. Researchers used the ATAC-seq sequencing method to discover nuclear chromatin structures in endothelial and smooth muscle cells, immune system monocytes, macrophages, NK / T, and B cells for cell-type-specific studies. Provided its own resources. Activity of cis-regulatory elements in disease-affected vessel walls.

This study showed that genetic risk variants associated with coronary artery disease are particularly rich in endothelium and endothelium-specific cis-regulatory elements. Smooth muscle cells, Shows that these cells play an important role in transmitting disease susceptibility.With chromatin accessibility mapping Gene expression data, Researchers were able to identify putative target genes for about 30% of all known loci associated with coronary artery disease. In addition, researchers performed genome-wide fine mapping of mutants to identify single nucleotide polymorphisms and associated target genes that are potentially responsible for more than 30 loci associated with coronary artery disease. I made it possible. The study also provided some examples of how chromatin accessibility and gene expression data can be used to predict target cells for which the function of disease-related gene alterations is transmitted within a tissue. This is an important step in helping us understand the actual functional importance of risk variants in the pathophysiology of coronary arteries. disease.. In the future, this information can be used to develop more effective, safer and more personalized treatments. Coronary artery disease..

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Many genes associated with the risk of coronary artery disease act through the liver

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For more information:
TiitÖrdetal, single-cell epigenomics and functional fine mapping of atherosclerosis GWAS loci, Circular research (2021). DOI: 10.1161 / CIRCRESAHA.121.318971

Provided by
University of Eastern Finland

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