Longevity & AgingBlood Cell Mutations May Quietly Fuel Heart Disease and Arterial Plaque Growth
As we age, blood stem cells accumulate DNA mutations that can let mutant clones expand, a state called clonal hematopoiesis of indeterminate potential (CHIP). This narrative review examines how CHIP, most often in DNMT3A, TET2, ASXL1 and JAK2, is linked to atherosclerosis, heart failure, thrombosis and worse outcomes after procedures such as TAVR. Mutant immune cells appear to amplify inflammation, notably through IL-1β and the NLRP3 inflammasome. Similar mutations have been found in arterial plaque, but whether vessel wall cells carry true somatic mutations is unproven. Causality is also debated, since inflammation may itself promote CHIP. The authors discuss CHIP as a risk biomarker and as a target for anti-inflammatory therapies such as canakinumab, colchicine and possibly metformin.
