Metabolomic profiling of ascending thoracic aortic aneurysms and dissections - Implications for pathophysiology and biomarker discovery.
Metabolomic profiling of ascending thoracic aortic aneurysms and dissections - Implications for pathophysiology and biomarker discovery.
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DOI：
10.1371/journal.pone.0176727
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Bernhard D
中科院分区：
文献类型：
--
作者：
Doppler C;Arnhard K;Dumfarth J;Heinz K;Messner B;Stern C;Koal T;Klavins K;Danzl K;Pitterl F;Grimm M;Oberacher H;Bernhard D
我们对升胸主动脉瘤（ATAA）发病机制的基本了解仍然非常有限，这阻碍了早期诊断、风险预测和治疗方案的制定。“组学”技术是揭示疾病引起的正常生理状态下组织变化的理想技术，但在该领域几乎没有应用。使用代谢组学方法，在这项研究中，作者试图确定对照组和各种形式的ATAAs之间的组织差异。使用靶向FIA-MS/MS代谢组学方法，我们分析并比较了年龄匹配对照组（n = 8）、二尖瓣主动脉瓣相关动脉瘤（n = 9）、三尖瓣主动脉瓣相关动脉瘤（n = 14）和三尖瓣主动脉瓣相关夹层（n = 6）的升胸主动脉壁组织代谢谱。鞘磷脂（SM） （OH） C22:2、SM C18:1、SM C22:1和SM C24:1的92种可检测代谢物中只有4种在对照组和BAV-A样本之间存在显著差异。在对照组和TAV-Diss样本之间，只有磷脂酰胆碱（PC）的比值为C32:1。重要的是，我们的分析显示，与对照组相比，BAV-A和TAV-Diss样本中的总鞘磷脂水平普遍增加。与对照组相比，BAV-A和TAV-Diss样本中鞘磷脂水平显著升高，这可能表明鞘磷脂酶活性和鞘磷脂酶-神经酰胺途径受到抑制，这可能导致组织再生受到抑制；疾病发生和发展的潜在基础。
Our basic understanding of ascending thoracic aortic aneurysm (ATAA) pathogenesis is still very limited, hampering early diagnosis, risk prediction, and development of treatment options. “Omics”-technologies, ideal to reveal tissue alterations from the normal physiological state due to disease have hardly been applied in the field. Using a metabolomic approach, with this study the authors seek to define tissue differences between controls and various forms of ATAAs. Using a targeted FIA-MS/MS metabolomics approach, we analysed and compared the metabolic profiles of ascending thoracic aortic wall tissue of age-matched controls (n = 8), bicuspid aortic valve-associated aneurysms (BAV-A; n = 9), tricuspid aortic valve-associated aneurysms (TAV-A; n = 14), and tricuspid aortic valve-associated aortic dissections (TAV-Diss; n = 6). With sphingomyelin (SM) (OH) C22:2, SM C18:1, SM C22:1, and SM C24:1 only 4 out of 92 detectable metabolites differed significantly between controls and BAV-A samples. Between controls and TAV-Diss samples only phosphatidylcholine (PC) ae C32:1 differed. Importantly, our analyses revealed a general increase in the amount of total sphingomyelin levels in BAV-A and TAV-Diss samples compared to controls. Significantly increased levels of sphingomyelins in BAV-A and TAV-Diss samples compared to controls may argue for a repression of sphingomyelinase activity and the sphingomyelinase-ceramide pathway, which may result in an inhibition of tissue regeneration; a potential basis for disease initiation and progression.