Abstract P340: The Role of Osteoclast-like Cells in Abdominal Aortic Aneurysm
Increasing evidence suggests that arterial calcification is the result of highly organized processes resembling those seen in bone which relies upon a delicate balance between mineral deposition and resorption by osteoblasts and osteoclasts, respectively. Osteoclast-like cells (OLCs) are derived from the monocyte/macrophage lineage and share osteoclast features such as the ability to dissolve extracellular matrix. Although osteoclastogenesis, the development of OLCs, has been reported to occur in calcified arteries, its potential role in the development of abdominal aortic aneurysm (AAA) has yet to be explored. Firstly, we obtained aortic tissues from patients undergoing surgical repair for AAA (N = 5) and aortic occlusive disease (N = 5). Alizarin-Red staining showed calcification in both aneurysmal and occlusive aorta. In contrast, OLCs, recognized as multi-nucleated cells positive for enzymatic TRAP staining, were identified only in aneurysmal aorta (100%, 5 of 5). A time course experiment in mouse calcium chloride-induced AAA (CaCl2AAA) showed similarities in both spatial and temporal patterns of calcium deposition and monocyte/macrophage accumulation starting 48 hours followed by OLCs formation peaked at 7 days after CaCl2injury. Secondly, we administered bisphosphonate (pamidronate disodium, 1.25 mg/kg, weekly), an inhibitor of osteoclasts, or normal saline as a control, intravenously to mice after CaCl2 injury (N = 5). Bisphosphonate-treated mice showed a significant reduction in aortic dilation compared to control mice after 7 and 42 days with mean fold change of 1.16 ± 0.04 (vs. 1.65 ± 0.05, P < 0.01) and 1.37 ± 0.12 (vs. 2.17 ± 0.08, P<0.01) respectively. We also studied the effect of bisphosphonate on “developed aneurysm” by delaying the injection of bisphosphonate until one week after the injury to allow the aneurysm to develop prior to injection (N = 5). The mice with delayed bisphosphonate injection also showed significant inhibition compared to the saline control at 42 days (1.56 ± 0.13 vs. 2.42 ± 0.06, P < 0.01). In conclusion, we have demonstrated the existence of OLCs in AAA. We also have demonstrated the inhibitory effect of bisphosphonate on aneurysm. These results indicate a novel approach for the pathogenesis and therapy of AAA.
- © 2011 by American Heart Association, Inc.