Variation in amount of wild-type transthyretin in different fibril and tissue types in ATTR amyloidosis.
Variation in amount of wild-type transthyretin in different fibril and tissue types in ATTR amyloidosis.
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DOI：
10.1007/s00109-010-0695-1
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Westermark P
中科院分区：
文献类型：
--
作者：
Ihse E;Suhr OB;Hellman U;Westermark P
家族性甲状腺素运载蛋白（TTR）淀粉样变性是由TTR基因突变引起的，尽管野生型（wt）TTR也掺入淀粉样纤维中。肝移植（LT）是该疾病的主要治疗方法，并且进行肝移植是为了从血浆中消除突变TTR。手术的结果是多种多样的;特别有问题的是在一些患者中观察到的进行性心肌病，推测是由wtTTR的持续掺入引起的。是什么决定了结果的差异尚不清楚。我们以前已经表明，两个结构不同的淀粉样纤维（有或没有片段化ATTR）中发现ATTRV 30 M患者。在这项研究中，我们调查了wtATTR在心脏和脂肪淀粉样蛋白的比例，从患者有原纤维类型。结果发现，心脏淀粉样蛋白更容易纳入wtTTR比脂肪淀粉样蛋白，提供了一个潜在的解释，为心脏组织的脆弱性，为继续淀粉样变性后LT。在心脏组织中，纤维与片段ATTR含有较高的重量比纤维没有，这表明继续纳入的wtTTR后LT，也许，可以更容易地发生在这些患者。在脂肪组织中，LT后重量比例的快速增加表明沉积物必须发生相当快的周转。原纤维类型之间的重量比例的差异后，LT，但不预LT，可能是由周转率的差异。总之，本研究进一步建立了两种纤维类型之间的基本差异，并表明它们在LT结果中的作用需要进一步研究。
Familial transthyretin (TTR) amyloidosis is caused by a mutation in the TTR gene, although wild-type (wt) TTR is also incorporated into the amyloid fibrils. Liver transplantation (LT) is the prevailing treatment of the disease and is performed in order to eliminate the mutant TTR from plasma. The outcome of the procedure is varied; especially problematic is a progressive cardiomyopathy seen in some patients, presumably caused by continued incorporation of wtTTR. What determines the discrepancy in outcome is not clear. We have previously shown that two structurally distinct amyloid fibrils (with or without fragmented ATTR) are found among ATTRV30M patients. In this study, we investigated the proportion of wtATTR in cardiac and adipose amyloid from patients having either fibril type. It was found that cardiac amyloid more easily incorporates wtTTR than adipose amyloid, offering a potential explanation for the vulnerability of cardiac tissue for continued amyloidosis after LT. In cardiac tissue, fibrils with fragmented ATTR contained a higher wt proportion than fibrils without, suggesting that continued incorporation of wtTTR after LT, perhaps, can take place more easily in these patients. In adipose tissue, a rapid increase in wt proportion after LT indicates that a rather fast turnover of the deposits must occur. A difference in wt proportion between the fibril types was seen post-LT but not pre-LT, possibly caused by differences in turnover rate. Conclusively, this study further establishes the basic dissimilarities between the two fibril types and demonstrates that their role in LT outcome needs to be further investigated.
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