摘要
腹主动脉瘤(AAA)是导致死亡的主要原因。目前,AAA的治疗主要是外科修复,目前还没有FDA批准的治疗AAA的药物,许多研究正在为AAA发现新的药物疗法。AAA的病理生理学被认为是导致动脉瘤壁退化的炎症和蛋白质溶解过程的复杂相互作用。动脉钙化是在AAA中观察到的,但其程度低于动脉闭塞性疾病,其发生方式与骨中矿物质沉积的过程类似。在动脉粥样硬化性斑块中,成骨细胞与矿物沉积有关。最近,在动脉粥样硬化性斑块中发现了破骨细胞样细胞-与成骨细胞相对应的破骨细胞。此外,在动脉粥样硬化性斑块中也存在破骨细胞样细胞,但在健康的主动脉壁中却不存在。破骨细胞样细胞分泌基质金属蛋白酶(MMP)-与动脉瘤壁变性有关的蛋白酶-可能与动脉瘤壁瘤的抑制程度有关。破骨细胞样细胞可能通过降低组织中mmps的水平来预防动脉瘤的进展。本文就AAA形成的病理生理学和药物治疗在AAA治疗中的作用进行了讨论,并强调了破骨细胞发挥关键作用的新假说。
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。
图形摘要
Current Drug Targets
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.
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Cite this article as:
Osteoclastogenesis in Abdominal Aortic Aneurysms: A New Therapeutic Target, Current Drug Targets 2018; 19 (11) . https://dx.doi.org/10.2174/1389450118666170925155044
DOI https://dx.doi.org/10.2174/1389450118666170925155044 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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