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Arterioscler Thromb Vasc Biol. 2019 Jun;39(6):1006-1017. doi: 10.1161/ATVBAHA.119.312141.

Genetic Insights Into Smooth Muscle Cell Contributions to Coronary Artery Disease.

Wong D1,2, Turner AW1, Miller CL1,2,3,4.

Author information

1
From the Center for Public Health Genomics (D.W., A.W.T., C.L.M.), University of Virginia, Charlottesville.
2
Department of Biochemistry and Molecular Genetics (D.W., C.L.M.), University of Virginia, Charlottesville.
3
Department of Biomedical Engineering (C.L.M.), University of Virginia, Charlottesville.
4
Department of Public Health Sciences (C.L.M.), University of Virginia, Charlottesville.

Abstract

Coronary artery disease is a complex cardiovascular disease involving an interplay of genetic and environmental influences over a lifetime. Although considerable progress has been made in understanding lifestyle risk factors, genetic factors identified from genome-wide association studies may capture additional hidden risk undetected by traditional clinical tests. These genetic discoveries have highlighted many candidate genes and pathways dysregulated in the vessel wall, including those involving smooth muscle cell phenotypic modulation and injury responses. Here, we summarize experimental evidence for a few genome-wide significant loci supporting their roles in smooth muscle cell biology and disease. We also discuss molecular quantitative trait locus mapping as a powerful discovery and fine-mapping approach applied to smooth muscle cell and coronary artery disease-relevant tissues. We emphasize the critical need for alternative genetic strategies, including cis/trans-regulatory network analysis, genome editing, and perturbations, as well as single-cell sequencing in smooth muscle cell tissues and model organisms, under both normal and disease states. By integrating multiple experimental and analytical modalities, these multidimensional datasets should improve the interpretation of coronary artery disease genome-wide association studies and molecular quantitative trait locus signals and inform candidate targets for therapeutic intervention or risk prediction.

KEYWORDS:

coronary artery disease; gene editing; genome-wide association study; quantitative trait loci; risk factors; vascular smooth muscle cells

PMID:
31043074
DOI:
10.1161/ATVBAHA.119.312141

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