脂类学
脂质体
病态的
纤维化
脂质代谢
钙化
主动脉瓣狭窄
心脏纤维化
内科学
生物
医学
病理
主动脉瓣
生物信息学
作者
Patricia Prabutzki,Michele Woelk,Julia Boettner,Zhixu Ni,Sarah Werner,Holger Thiele,Juergen Schiller,Petra Büttner,Florian Schlotter,Maria Fedorova
标识
DOI:10.1101/2024.08.07.606946
摘要
Fibro-calcific aortic valve disease (FCAVD) is the most common valvular heart disease manifesting in pathological fibro-calcific remodeling of the aortic valve (AV) leaflets, ultimately leading to aortic stenosis. Although lipid dysmetabolism is a driver of FCAVD pathogenesis, the molecular details of the AV lipidome remodeling upon fibrosis and calcification remain largely unknown. Here, we employed advanced lipidomics technologies for deep quantitative profiling of metabolic trajectories in human tricuspid and bicuspid AVs at different pathological stages. Specific extrinsic and intrinsic lipid trends, accompanying the development of fibrosis and calcification, were identified. Importantly, significant differences in lipid signatures between male and female individuals were demonstrated and were attributable to altered sphingolipid metabolism. Taken together, deep lipidomics profiling allowed to identify major molecular events and revealed a high extent of sex-dimorphism in lipidomics signatures of human FCAVD.
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