As people age, it has been shown that mutations occur in hematopoietic stem cells, which develop into different types of blood cells. These mutations are found to increase around the age of 40 and continue to do so from then on. While these mutations, called clonal hematopoiesis of indeterminate potential (CHIP), have been shown to be associated with an increased risk of atherosclerotic cardiovascular disease, it is not clear how or why this association takes place.
The National Institutes of Health’s Heart, Lung, and Blood Institute has recently awarded Dr. Christie Ballantyne, professor of medicine and chief of the sections of cardiology and Cardiovascular Research at Baylor College of Medicine, a $6 million grant to begin research to better understand how CHIP contributes to atherosclerotic cardiovascular diseases.
He will be collaborating with Dr. Richard A. Gibbs, director of the Human Genome Sequencing Center at Baylor, Dr. Eric Boerwinkle, dean of UTHealth School of Public Health and associate director of the Human Genome Sequencing Center at Baylor and Pradeep Natarajen and other researchers at Massachusetts General Hospital and the Broad Institute of MIT and Harvard.
This research team has previously shown that the presence of CHIP is associated with prevalent myocardial infarction, the frequency of CHIP increases with age, and the presence of CHIP predicts future myocardial infarction. This clinical data along with basic research suggests that CHIP has a direct causal influence on development of clinical atherosclerotic cardiovascular disease.
Using this information, Ballantyne and his collaborators will work to understand if CHIP relates to future risk for incidence of certain cardiovascular diseases, why some individuals develop these mutations but are not affected by disease, whether CHIP represents a causal risk factor for atherosclerotic cardiovascular disease and whether inflammatory mediators are associated with the presence of CHIP and the development of cardiovascular events.
“As we increase our understanding of the development of CHIP with aging, CHIP has the potential to be the most important nontraditional risk factor underlying atherosclerotic cardiovascular disease with increased age,” Ballantyne said.
Data used in the study will come from two long-term studies, the Atherosclerosis Risk in Communities Study and UK Biobank. The information provided by these studies includes exome sequences, which are used to analyze the presence of CHIP, blood biomarkers, proteomics, and data regarding atherosclerotic cardiovascular disease events monitored on a long-term basis.
CHIP has also been shown to be associated with certain types of cancers. As the study progresses, Ballantyne hopes this will lead to future collaborations to uncover how CHIP influences both heart disease and cancer as we age.