Osteoprotegerin Prevents Development of Abdominal Aortic Aneurysms.
Osteoprotegerin Prevents Development of Abdominal Aortic Aneurysms.
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DOI：
10.1371/journal.pone.0147088
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yoshizumi M
中科院分区：
文献类型：
--
作者：
Bumdelger B;Kokubo H;Kamata R;Fujii M;Yoshimura K;Aoki H;Orita Y;Ishida T;Ohtaki M;Nagao M;Ishida M;Yoshizumi M
腹主动脉瘤(AAA)通常发生在老年人中，伴随着破裂的风险和随后的高死亡率。建立预防腹主动脉硬化的药物治疗需要进一步了解这种疾病的分子发病机制。本报告详细介绍了骨保护素(OPG)可能通过抑制肿瘤坏死因子相关的凋亡诱导配体(TRAIL)而参与预防AAA的可能。在CaCl2诱导的AAA模型中，与野生型小鼠相比，OPG基因敲除(KO)小鼠中膜弹性纤维被破坏，内径和外径均显著增加。免疫组织化学分析发现，TRAIL在培养上清液中表达上调。在体外培养体系中，OPG可抑制TRAIL诱导的SMC基质金属蛋白酶-9的表达及TRAIL对SMC的趋化作用。提示OPG可能通过对TRAIL的拮抗作用，在AAA的发生发展中起到预防作用。
Abdominal aortic aneurysms (AAAs), which commonly occur among elderly individuals, are accompanied by a risk of rupture and subsequent high mortality. Establishment of medical therapies for the prevention of AAAs requires further understanding of the molecular pathogenesis of this condition. This report details the possible involvement of Osteoprotegerin (OPG) in the prevention of AAAs through inhibition of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In CaCl2-induced AAA models, both internal and external diameters were significantly increased with destruction of elastic fibers in the media in Opg knockout (KO) mice, as compared to wild-type mice. Moreover, up-regulation of TRAIL expression was observed in the media by immunohistochemical analyses. Using a culture system, both the TRAIL-induced expression of matrix metalloproteinase-9 in smooth muscle cells (SMCs) and the chemoattractive effect of TRAIL on SMCs were inhibited by OPG. These data suggest that Opg may play a preventive role in the development of AAA through its antagonistic effect on Trail.