Lipidomic signatures of aortic media from patients with atherosclerotic and nonatherosclerotic aneurysms

Kosuke Saito,Yutaka Iba,Sayaka Muto,Hiroaki Sasaki,Hatsue Ishibashi-Ueda,Hitoshi Ogino,Keiko Maekawa,Masaki Ishikawa,Tsukasa Osaki,Naoto Minamino,Hitoshi Matsuda,Yoshiro Saito,Mitsuhiro Nishigori,Yoshihiko Ikeda,Hiroaki Yagi,Kenji Minatoya

doi:10.1038/s41598-019-51885-4

Abstract

Aortic aneurysms are associated with fatal aortic rupture. Current therapeutic approaches are limited to implantation of aortic prostheses and stent-grafts; no effective drugs are available because the pathogenic mechanisms of aortic aneurysms remain unclear. Here, we aimed to elucidate the molecular mechanisms of the initiation and progression of aortic aneurysm by lipidomics. We performed lipidomics analyses of lipids in the aortic media of normal, border, and aneurysm areas from patients with thoracic atherosclerotic aortic aneurysm (N = 30), thoracic nonatherosclerotic aortic aneurysm (N = 19), and abdominal atherosclerotic aortic aneurysm (N = 11) and from controls (N = 8) using liquid chromatography and mass spectrometry. Significant alterations were observed in the lipid profiles of patients with atherosclerotic aortic aneurysms and to a lesser extent in those with nonatherosclerotic aneurysms. Increased triacylglycerols (TGs) and decreased ether-type phosphatidylethanolamines (ePEs) were observed throughout the normal, border, and aneurysm areas of thoracic and abdominal atherosclerotic aortic aneurysms. Prostaglandin D2 increased, but ePEs and TGs decreased in normal areas of thoracic atherosclerotic aortic aneurysms and thoracic nonatherosclerotic aortic aneurysms compared with the control tissues. These findings expand our knowledge of metabolic changes in aortic aneurysms and provide insights into the pathophysiology of aortic aneurysms.

Highlights

Aortic aneurysms are associated with fatal aortic rupture
Patients with thoracic atherosclerotic aortic aneurysm (TAAA) and abdominal atherosclerotic aortic aneurysm (AAAA) showed no differences in age; patients with TAAA and AAAA were older than the control patients with control normal thoracic aorta (CNTA) (p < 0.001 for TAAA, p = 0.004 for AAAA; Table 1), since all the control patients without vascular disease had received age-restricted heart transplants
The average maximum aneurysmal diameters of TAAA, thoracic nonatherosclerotic aortic aneurysm (TNAA), and AAAA, were 56.5 ± 1.2, 54.5 ± 1.5, and 57.0 ± 3.1 mm, respectively, and no differences were observed among their diameters

Summary

Introduction

Aortic aneurysms are associated with fatal aortic rupture. Current therapeutic approaches are limited to implantation of aortic prostheses and stent-grafts; no effective drugs are available because the pathogenic mechanisms of aortic aneurysms remain unclear. Prostaglandin D2 increased, but ePEs and TGs decreased in normal areas of thoracic atherosclerotic aortic aneurysms and thoracic nonatherosclerotic aortic aneurysms compared with the control tissues These findings expand our knowledge of metabolic changes in aortic aneurysms and provide insights into the pathophysiology of aortic aneurysms. To identify target molecules for the development of therapies and drugs, the aortic media of aortic aneurysms is a promising target tissue and can be subjected to Omics analyses to elucidate the pathophysiology of atherosclerotic aortic aneurysms Lipids, such as phosphoglycerolipids, sphingolipids, and neutral lipids, play key roles in a variety of physiological and biological processes as membrane constituents, energy sources, and second messengers[8,9,10]. Our results provided fundamental information for elucidating the molecular mechanisms of atherosclerotic aortic aneurysms and identifying potential drug targets for the treatment of this disease

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