Osteoclastogenesis in Abdominal Aortic Aneurysms: A New Therapeutic Target

Title:Osteoclastogenesis in Abdominal Aortic Aneurysms: A New Therapeutic Target

Volume: 19 Issue: 11

Author(s): Alexander D. Leung and Dai Yamanouchi*

Affiliation:

• Department of Surgery,Division of Vascular Surgery,University of Wisconsin,600 Highland Avenue, G5/319Madison, WI 53792,United States

Keywords: Abdominal aortic aneurysm, osteoclastogenesis, osteoclast-like cells, zoledronate, medical therapy, aneurysm repair.

Abstract: 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.

Cite this article as:

Leung D. Alexander and Yamanouchi Dai *, Osteoclastogenesis in Abdominal Aortic Aneurysms: A New Therapeutic Target, Current Drug Targets 2018; 19 (11) . https://dx.doi.org/10.2174/1389450118666170925155044