Most deaths in the world are caused by damage to the cardiovascular system, with atherosclerosis (inflammation of large vessels) representing the main underlying cause of cardiovascular disease (CVD).
Clonal Hematopoiseis (CH) represents a clonal expansion of blood cells arising from somatic mutations in genes that confer a growth advantage to hematopoietic stem cells (HSCs) and were therefore associated with the onset of blood cancers.
Members form our Network demonstrated that CH increases in frequency from age 40 onwards, is present in >10% of people aged >70 and increases risk of myocardial infarction by at least 2-3 fold, suggesting that CH could be the most important non-traditional risk factor underlying atherosclerotic CVD.
CH usually involves mutations in one of four genes producing loss of function in epigenetic modifiers (TET2, ASXL1 or DNMT3A) or increased hematopoietic signaling (JAK2) that typically alter the function rather than the number of inflammatory cells, including macrophages, monocytes, neutrophils and platelets.
We propose that CH mutations has adverse effects on the functions of these cells that could lead to athero-thrombosis. Our Network will use multiple approaches to better understand how the atherosclerotic plaque forms, its relation with CH, and examine strategies to alleviate vascular inflammation and CVD.