Title:Osteoclastogenesis in Abdominal Aortic Aneurysms: A New Therapeutic Target
Volume: 19
Issue: 11
关键词:
腹主动脉瘤，破骨发生，破骨细胞样细胞，唑来膦酸盐，药物治疗，动脉瘤修复。
摘要: Abdominal aortic aneurysms (AAA) are a major cause of death. Currently, the mainstay of
treatment for AAA is surgical repair and there are no FDA approved medical therapies for AAA.
Much research is in progress to discover new medical therapies for AAA. The pathophysiology of
AAA is understood to be a complex interplay of inflammatory and proteolytic processes that degenerate
the aneurysm wall. Arterial calcification, which is observed in AAA but to a lesser extent than in
arterial occlusive disease, occurs in a highly regulated manner in a similar process as mineral deposition
in bone. Osteoblasts-like cells are responsible for mineral deposition in atherosclerotic plaques.
Recently, osteoclast-like cells – the catabolic counterpart to osteoblasts – were discovered in atherosclerotic
plaques. Additionally, osteoclast-like cells are present in the wall of AAA but not in healthy
aortas. Osteoclast-like cells secrete matrix metalloproteinases (MMP) – proteases implicated in arterial
aneurysm wall degeneration – and may contribute to the degredation of the aneurysm wall. Inhibiting
osteoclast-like cells may prevent aneurysm progression by reducing tissue levels of MMPs. In this review,
we discuss the pathophysiology of AAA formation and the current role of medical therapy in
treatment of AAA. Furthermore, we highlight the emerging hypothesis that osteoclasts play a key role
in the development of AAA and discuss therapies to inhibit osteoclastogenesis in AAA.
