Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 43, Issue 1, Pages 3-14Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.122.318181
Keywords
cardiovascular disease; clonal hematopoiesis; coronary artery disease; genetics; inflammation
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Chronologic age is the main risk factor for coronary artery disease, and age-related subclinical leukemogenic mutations in blood cells have been found to play a surprising role in this disease. These mutations occur in genes such as DNMT3A, TET2, ASXL1, and JAK2. Studies on mice and humans have shown the involvement of inflammatory pathways in linking clonal hematopoiesis with coronary artery disease. Further analysis using larger, longitudinal, and multiomics approaches is providing mechanistic insights. These observations have expanded our understanding of the genetic basis of coronary artery disease, connecting it with hematologic neoplasia. They also have implications for the development of novel precision medicine approaches for this disease.
Chronologic age is the dominant risk factor for coronary artery disease but the features of aging promoting coronary artery disease are poorly understood. Advances in human genetics and population-based genetic profiling of blood cells have uncovered the surprising role of age-related subclinical leukemogenic mutations in blood cells, termed clonal hematopoiesis of indeterminate potential, in coronary artery disease. Such mutations typically occur in DNMT3A, TET2, ASXL1, and JAK2. Murine and human studies prioritize the role of key inflammatory pathways linking clonal hematopoiesis with coronary artery disease. Increasingly larger, longitudinal, multiomics analyses are enabling further dissection into mechanistic insights. These observations expand the genetic architecture of coronary artery disease, now linking hallmark features of hematologic neoplasia with a much more common cardiovascular condition. Implications of these studies include the prospect of novel precision medicine paradigms for coronary artery disease.
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