Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?
Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?
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DOI：
10.1186/1750-1172-7-70
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发表时间：
2012-09-22
影响因子：
3.7
通讯作者：
Boerkoel, Cornelius F.
中科院分区：
文献类型：
--
作者：
Morimoto, Marie;Yu, Zhongxin;Boerkoel, Cornelius F.
背景：动脉硬化和肺气肿发生在Schimke免疫性骨发育不良(SIOD)患者中，SIOD是一种由SMARCAL1双等位基因突变引起的多系统疾病(SWI/SNF相关、基质相关、肌动蛋白依赖的染色质调节因子，亚家族a-like 1)。然而，血管和肺部疾病在SIOD中发生的机制尚不清楚。方法：我们回顾了65例SMARCAL1突变患者的记录。结果：63例患者中32例有动脉硬化征象，51例中有3例有肺气肿征象。动脉硬化以内膜、中膜增生、平滑肌细胞增生、弹性蛋白纤维碎裂、排列紊乱为特征，肺部疾病以全小叶气腔扩大为特征。SMARCAL1在动脉和肺组织中的表达与细胞自主性紊乱一致，SIOD患者的主动脉和肺组织中弹性蛋白的表达减少，弹性蛋白基因表达调节因子的表达发生改变。结论：首次对SIOD的血管和肺部并发症进行了全面的研究，表明这些并发症通常会导致发病率和死亡率，可能是由于弹力生成受损引起的。此外，SMARCAL1缺陷对弹性蛋白表达的影响为理解SIOD的其他特征提供了一个模型。
Background: Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown.Methods: We reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients.Results: Thirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression.Conclusions: This first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD.