THE ROLE OF TET2 MUTATIONS IN THE DEVELOPMENT OF CHIP-ASSOCIATED ATHEROSCLEROSIS

Abstract

TET2 (Ten-Eleven Translocation 2) mutations are among the most common in CHIP (Clonal Hematopoiesis of Indeterminate Potential) and the most clinically significant in cardiology. Loss of TET2 function leads to hyperactivation of the NLRP3 (NOD-like receptor family pyrin domain containing protein 3) inflammasome in macrophages and overproduction of the interleukins IL-1β, IL-6, and TNF-α, which causes chronic vascular inflammation. This inflammation contributes to endothelial dysfunction, the formation of unstable atherosclerotic plaques, and increases the risk of myocardial infarction and stroke by 2–4 times. Given these findings, it is suggested that CHIP can be considered a new independent risk factor for atherosclerosis, and patients with TET2-mutant CHIP may be the best candidates for therapy with IL-1β inhibitors.