Abstract
ObjectiveOur 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.MethodsUsing 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).ResultsWith 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.ConclusionsSignificantly 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.
Highlights
Aneurysms in general represent a Damocles sword in the classical sense for patients diagnosed with one of these diseases, and a hidden version of the sword for the general population
Our analyses revealed a general increase in the amount of total sphingomyelin levels in bicuspid aortic valve-associated aneurysms (BAV-A) and TAV-Diss samples compared to controls
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
Summary
Aneurysms in general represent a Damocles sword in the classical sense for patients diagnosed with one of these diseases, and a hidden version of the sword for the general population. As aneurysms usually occur in the absence of (clear) symptoms, the first detection is often a matter of chance, e.g. as a result of clinical imaging. Due to the devastating consequences of aneurysm-associated arterial dissections and ruptures there is significant interest in the development of tests for early diagnosis. The pathogenesis of many forms of aneurysms is not clear, which has so far hampered personalization of aneurysm treatment. The general wish is to better define the individual time-point when surgical intervention is indicated, and even more, to have specific non-surgical options to slow down or stop disease progression. Early diagnosis and improved treatment need a better understanding of these diseases
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