Aging Dis. 2026 Feb 16. doi: 10.14336/AD.2025.1422. Online ahead of print.
ABSTRACT
Abdominal aortic aneurysm (AAA) is a degenerative vascular disease with a high mortality rate of rupture, yet effective pharmacological interventions to delay its progression or prevent rupture remain unavailable. Vascular calcification (VC), a prominent pathological feature of AAA, exhibits a paradoxical role. Clinical and biomechanical studies confirm that VC exerts a dual effect: it accelerates AAA progression by inducing local stress concentration, while simultaneously providing mechanical stability through global load-sharing effect. This functional paradox may stem from a dynamic imbalance between anabolic and catabolic processes at the cellular and molecular levels. Specifically, microcalcification is mediated by the osteogenic transition of vascular smooth muscle cells (VSMCs), whereas the osteoclastic transformation of macrophages contributes to the ultimate matrix degradation. Furthermore, the impacts of vascular aging, sex differences, and metabolic dysregulation between VC and AAA are briefly summarized. This review systematically synthesizes multi-scale evidence to elucidate the dual role of VC in AAA progression, proposing a non-linear dynamic trajectory linking microcalcification initiation to macrocalcification maturation during aneurysm progression. Finally, it also emphasizes that future research should shift from assessing static calcification burden toward dynamically monitoring the metabolic activity of microcalcification, as well as discussing emerging therapeutic targets. This perspective offers new insights for early risk stratification and precise intervention in AAA.
PMID:41701877 | DOI:10.14336/AD.2025.1422