This study found that a metabolomic strategy could be used to identify potential metabolic markers of AD and to explore the metabolic pathways related to its occurrence. We carried out a comprehensive metabolomic evaluation of 30 AD patients. Metabolic phenotypes revealed significant pattern differences between patients with AD and HC, suggesting that AD may involve some metabolic disturbance, such as phospholipid metabolism disorder.
Patients with AD have a higher heart rate and D-dimer6. Except for heart rate at admission and D-dimer levels, the clinical baseline data between the two groups of patients was the same.
Analysis of metabolic pathways enriched by 71 different metabolites showed that the different metabolites were involved in five pathways, including choline metabolism in cancer, neuroactive ligand-receptor interaction, glycerophospholipid metabolism, sphingolipid metabolism, and ether lipid metabolism. KEGG analysis showed oxidative stress and lipid transport and metabolism were significantly implicated.
Compared to HCs, patients with AD had down-regulated N2-gamma-glutamylglutamine(γ-glu) and taurine, both of which play a key role in amino acid and fat metabolism. especially taurine. There is evidence that it affects mitochondrial bioenergetics, counteracts lipid peroxidation and even increases cellular antioxidant defense in response to inflammation7.
The patients with AD also had up-regulated propionyl carnitine and PC(20:4(5Z,8Z,11Z,14Z)/15:0). Propionyl carnitine is a free radical that can produce positive effects on endothelial function and protect endothelia from oxidative stress8. The increase in propionyl carnitine may be related to the repair of endometria after aortic dissection tear.
The PC(20:4(5Z,8Z,11Z,14Z)/15:0) is the precursor of phospholipids, which can decholine to produce phospholipids through a series of metabolic reactions in the body. The phospholipid metabolism disorder may be closely related to the occurrence of AD.
The diagnosis of acute AD relies on imaging such as vascular enhanced CT.9 For community hospitals that lack relevant equipment, this is not conducive for the early diagnosis of acute aortic dissection, so finding a high-sensitivity metabolite of AD would be important for rescuing these patients.
This study identified and validated the signature consisting of four differential metabolites known to be related to AD pathogenesis that can accurately distinguish AD patients from healthy controls. Despite limitations such as the small sample size, evidence showed that metabolites may be adopted as markers for the diagnosis of AD.
Aortic dissection is caused by a tear in the intimal layer of the aorta, resulting in the separation of the layers of the aortic wall10. Extracellular matrix degradation and inflammation may contribute to the occurrence of the disease, but the precise trigger of aortic dissections is still unknown2. In the metabolic pathways enriched with differential metabolites, this study constructed a simple metabolic pathway model, where choline promoted the increase of phospholipids through transport proteins and second messengers. Phospholipids activated downstream pathways including cell-cycle progression, proliferation migration angiogenesis and actin reorganization, but PC(20:4(5Z,8Z,11Z,14Z)/15:0) controls and regulates other pathways by negative feedback.
Previous studies considered that AD would activate cell-cycle progression11, 12 and this is consistent with these results. It is considered that the inflammatory response was important for AD13–15, leading to smooth muscle cells (SMCs) expression of secretory molecules, including cytokines and extracellular matrix (ECM) molecules and prompting the proliferative capacity16. Inflammatory cells, such as lymphocytes and macrophages, secrete multiple inflammatory cytokines to promote vascular adhesion molecule expression17, eventually leading to proliferation migration angiogenesis. Inflammatory cells also contribute to the apoptosis of SMCs in the aortic artery and lead to medial degradation, exacerbating intimal tears18.
Actin is an important protein, playing a critical role in many cellular functions and the interaction of actin with myosin forms the basis of muscle contraction19. In human aortic smooth muscle cells, smooth muscle α-actin (α-SMA) participated in filamentous actin formation and its expression can facilitate stress fiber formation and cell contraction in human aortic smooth muscle cells20. During the development of AD, smooth muscle cells may switch occurrence of phenotype21,lead to actin reorganization and cause smooth muscle cell apoptosis21, eventually causing the occurrence and progression of aortic dissection.
This study had some limitations. It failed to functionally verify the differential metabolites further. The sample size was small and could be further expanded in the future.