Abstract
Aortic dissection (AD) is a catastrophic cardiovascular emergency with a poor prognosis, and little preceding symptoms. Abnormal lipid metabolism is closely related to the pathogenesis of AD. However, comprehensive lipid alterations related to AD pathogenesis remain unclear. Moreover, there is an urgent need for new or better biomarkers for improved risk assessment and surveillance of AD. Therefore, an untargeted lipidomic approach based on ultra-high-performance liquid chromatograph-mass spectrometry was employed to unveil plasma lipidomic alterations and potential biomarkers for AD patients in this study. We found that 278 of 439 identified lipid species were significantly altered in AD patients (n = 35) compared to normal controls (n = 32). Notably, most lipid species, including fatty acids, acylcarnitines, cholesteryl ester, ceramides, hexosylceramides, sphingomyelins, lysophosphatidylcholines, lysophosphatidylethanolamines, phosphatidylcholines, phosphatidylinositols, diacylglycerols, and triacylglycerols with total acyl chain carbon number ≥54 and/or total double bond number ≥4 were decreased, whereas phosphatidylethanolamines and triacylglycerols with total double bond number <4 accumulated in AD patients. Besides, the length and unsaturation of acyl chains in triacylglycerols and unsaturation of 1-acyl chain in phosphatidylethanolamines were decreased in AD patients. Moreover, lysophosphatidylcholines were the lipids with the largest alterations, at the center of correlation networks of lipid alterations, and had excellent performances in identifying AD patients. The area under the curve of 1.0 and accuracy rate of 100% could be easily obtained by lysophosphatidylcholine (20:0/0:0) or its combination with lysophosphatidylcholine (17:0/0:0) or lysophosphatidylcholine (20:1/0:0). This study provides novel and comprehensive plasma lipidomic signatures of AD patients, identifies lysophosphatidylcholines as excellent potential biomarkers, and would be beneficial to the pathogenetic study, risk assessment and timely diagnosis and treatment of AD.
Highlights
Aortic dissection (AD), defined as the progressive separation of aortic wall layers, is a catastrophic cardiovascular emergency with an acute onset, a poor prognosis, and little preceding symptoms [1, 2]
278 of 439 identified lipid species were found to be significantly altered in patients with AD compared to normal controls, including 42 fatty acids (FAs), 13 acylcarnitines (ACs), 1 cholesteryl ester (CE), 7 ceramides (Cers), 5 hexosylceramides (HexCers), 40 SMs, 24 lysophosphatidylcholines (LPCs), 6 lysophosphatidylet hanolamines (LPEs), 59 phosphatidylcholines (PCs), 9 phos phatidylethanolamines (PEs), 11 phosphatidylinositols (PIs), 17 diacylglycerols (DGs), and 44 triacylglycerols (TGs) (Figure 2A; Supplementary Table 2)
The results showed that when LPC (20:0/0:0), LPC (17:0/0:0), LPC (18:0/0:0), LPC (18:1/0:0), LPC (16:0/0:0), LPC (20:1/0:0), LPC (20:2/0:0), LPC (15:0/0:0), and LPC (22:0/0:0) were used as the potential biomarker, respectively, the area under the curve could be above 0.99, and the accuracy rate could be above 95%, demonstrating that above 9 LPCs had excellent diagnostic performances in identifying patients with AD from normal controls
Summary
Aortic dissection (AD), defined as the progressive separation of aortic wall layers, is a catastrophic cardiovascular emergency with an acute onset, a poor prognosis, and little preceding symptoms [1, 2]. Targeted serum metabolomics discovered that the trimethylamine N-oxide level was significantly higher, whereas those of choline, betaine, and carnitine were significantly lower in patient with AD compared to normal controls, and that trimethylamine N-oxide had significant positive correlations with parameters on AD severity, including interleukin-6, D-dimer, C-reactive protein, and maximum aortic diameter on admission [6]. The trimethylamine N-oxide level was significantly increased in AD patients with plaque rupture compared to AD patients without plaque rupture, and not affected by the incidence of hypertension [6]. Knockout of vascular smooth muscle cell-specific E-prostanoid receptor 4 gene induced AD in angiotensin II-infused mice with severe degradation of aortic elastic fiber, smooth muscle cell dedifferentiation, increased vascular NADPH oxidase 1 activity, reactive oxygen species generation, macrophage infiltration, matrix metalloproteinase-2/9 levels, and monocyte chemoattractant protein-1 expression, and higher blood pressure [7]. Phospholipases and unsaturated fatty acids (FAs) were demonstrated to have vital roles in the pathogenesis of AD [8]
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