Supplementary Elevated triglycerides predispose patients to aortic dissection by increasing inflammasome-induced pyroptosis

Abstract

Abstract Aortic dissection (AD) is an acute and life-threatening disease that requires invasive therapy once the aorta has been lacerated. Although several studies have suggested that abnormal lipid metabolism is associated with the development of AD, there are no studies examining the specific mechanisms by which abnormal lipid metabolism contributes to the development of aortic dissection. The aim of this study was to investigate in depth the important role of abnormal lipid metabolism in the development of AD and its possible underlying mechanism. We applied lipid metabolism sequencing and transcriptome sequencing to detect lipid and pathway changes in the blood of AD patients and controls. We applied an AD model via β-aminopropionitrile (BAPN) treatment, and at the same time, we observed the effect of a high-TG environment on AD occurrence in vivo via high-fructose feed. In addition, we applied GSDME knockout mice to reduce GSDME expression. We found that all the upregulated lipids in the serum of AD patients were triglycerides, while the downregulated lipids included mainly sphingomyelin, ceramide, and lysophosphatidylcholine. Lipid metabolism sequencing and transcriptome sequencing revealed differences in serum lipid and proteins related to inflammation. Moreover, in BAPN model mice, elevated triglyceride levels increase the occurrence of aortic dissection, whereas GSDME knockdown inhibits the occurrence of AD but does not inhibit the inflammatory response in the aorta. Elevated triglycerides induce increased pyroptosis in the aortic wall by increasing the inflammatory response in the vasculature, which leads to phenotypic transformation of vascular smooth muscle cells, allowing for an increased incidence of AD.