Proteomic and phosphoproteomic analyses of myectomy tissue reveals difference between sarcomeric and genotype-negative hypertrophic cardiomyopathy.

Proteomic and phosphoproteomic analyses of myectomy tissue reveals difference between sarcomeric and genotype-negative hypertrophic cardiomyopathy.
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DOI:
10.1038/s41598-023-40795-1
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发表时间:
2023-09-01
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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肥厚型心肌病(HCM)是一种遗传异质性疾病,约有一半的病例在遗传上是难以捉摸的或非遗传性的。具有阳性基因测试(HCMSarc)的HCM患者比具有阴性基因测试(HCMNeg)的HCM患者出现更早并且具有更严重的疾病。我们假设这些差异可能是由于和/或反映了两组之间的蛋白质组学和磷酸化蛋白质组学差异。对15份HCMSarc、8份HCMNeg和7份对照样品进行TMT标记的质谱分析。HCMSarc和HCMNeg之间有243个蛋白质差异表达,257个蛋白质差异磷酸化。基因型之间约90%的途径改变是在疾病相关的途径和HCMSarc显示增强的蛋白质组和磷酸蛋白质组的改变,在这些途径。因此,我们表明HCMSarc具有观察到的增强的蛋白质组和磷酸蛋白质组失调,这可能有助于更严重的疾病表型。
Hypertrophic cardiomyopathy (HCM) is a genetically heterogenous condition with about half of cases remaining genetically elusive or non-genetic in origin. HCM patients with a positive genetic test (HCMSarc) present earlier and with more severe disease than those with a negative genetic test (HCMNeg). We hypothesized these differences may be due to and/or reflect proteomic and phosphoproteomic differences between the two groups. TMT-labeled mass spectrometry was performed on 15 HCMSarc, 8 HCMNeg, and 7 control samples. There were 243 proteins differentially expressed and 257 proteins differentially phosphorylated between HCMSarc and HCMNeg. About 90% of pathways altered between genotypes were in disease-related pathways and HCMSarc showed enhanced proteomic and phosphoproteomic alterations in these pathways. Thus, we show HCMSarc has enhanced proteomic and phosphoproteomic dysregulation observed which may contribute to the more severe disease phenotype.
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