Study Links Clonal Hematopoiesis to Accelerated Abdominal Aortic Aneurysm Growth

A study published on April 15, 2026, in the Journal of Clinical Investigation reported that clonal hematopoiesis of indeterminate potential (CHIP) is linked to faster expansion of abdominal aortic aneurysms (AAAs).

The research, conducted by a team including Jun Yonekawa and colleagues, analyzed patient specimens and found a high prevalence of CHIP-associated mutations correlating with accelerated aneurysm growth. These mutations, particularly in the Tet2 gene, were shown to drive immune cells toward an osteoclast-like state that produces matrix-degrading enzymes.

The study used targeted ultradeep sequencing on specimens from patients with AAAs.

Results indicated that individuals with CHIP experienced quicker aneurysm dilation over a one-year period compared to those without such mutations. This association highlights CHIP as a potential risk factor for AAA progression, which is an age-related condition leading to aortic dilation and high mortality risk from rupture.

In experiments, researchers modeled CHIP by transplanting Tet2-deficient bone marrow into mice prone to aneurysms.

These mice developed significantly larger aortic dilations when aneurysms were induced with angiotensin II. The Tet2-deficient macrophages in these models expressed higher levels of acid phosphatase 5 and matrix metalloproteinase 9, contributing to tissue destruction. Genetic and pharmacological inhibition of the osteoclast-like differentiation process reduced aneurysm growth in the models.

Specifically, targeting the RANK/RANKL pathway with drugs like alendronate and denosumab suppressed the destructive effects. S.

increases with age, affecting more than 10% of individuals over 65 years old.

The study extends prior associations of CHIP with cardiovascular diseases such as atherosclerosis and heart failure to include AAAs. By identifying macrophage reprogramming as a key mechanism, the research points to modifiable pathways for preventing aneurysm progression. No nonsurgical treatments currently exist for AAAs, which progress silently and carry high mortality upon rupture.

The findings suggest that screening for CHIP mutations could identify at-risk patients, and existing therapies might offer preventive options. Further clinical studies are needed to validate these approaches in humans.