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非传统风险冠心病中的脂质组、中心碳代谢物与睡眠节律:一项探索性初步研究。

Lipidome, central carbon metabolites, and sleep rhythm in coronary heart disease with nontraditional risks: An exploratory pilot study.

作者信息

Xia Yan, Chen Ao, Lu Danbo, Jin Jiayu, Yin Ming, Wang Yinman, Zhang Yiqi, Lu Ying, Ma Jiaqi, Deng Lixiang, Zhang Peipei, Li Su, Yang Hongbo, Li Chenguang, Lu Hao, Chen Zhangwei, Qian Juying, Ge Junbo

机构信息

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Shanghai, 200032, China.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai, 200032, China.

出版信息

Heliyon. 2023 Mar 24;9(4):e14827. doi: 10.1016/j.heliyon.2023.e14827. eCollection 2023 Apr.

Abstract

AIMS

Altered lipid, energy metabolism and sleep disorders had been linked with coronary heart disease (CHD), however, the metabolic signatures and sleep rhythm in non-obstructive coronary atherosclerosis-CHD remain unclear. This pilot study aims to investigate the lipidome and central carbon metabolites profiles and associated sleep characteristics among CHD patients without traditional risk factors.

METHODS

From January to July 2021, 15 CHD patients and 15 healthy controls were randomly selected from the cardiology unit of Zhongshan Hospital, Shanghai. A total of 464 lipids and 45 central carbon metabolites (CCM) were quantified in blood plasma. Metabolic signatures were selected through orthogonal projections to latent structures discriminant analysis (OPLS-DA) and principal component analysis (PCA) was conducted to link the profiles of identified metabolites with CHD risk, sleep patterns, cardiometabolic traits and cardiac electrophysiologic parameters.

RESULTS

Using OPLS-DA, we identified 40 metabolites (variable influence on projection >1) that were altered in CHD patients, with 38 lipids, including 25 triacylglycerols (TAGs), 8 diacylglycerols (DAGs), being elevated and two CCM metabolites (i.e., succinic acid and glycolic acid) being reduced. Using PCA, four principal components (PCs) were identified and associated with increased risk of CHD. Specifically, one standard unit increasement in the PC that was characterized by high levels of DAG (18:1) and low succinic acid and the PC that was characterized by high levels of two sphingomyelins [SM (26:0) and SM (24:0)] was associated with 21% [odds ratio (OR) = 1.21, 95% CI: 1.02,1.43] and 14% (OR = 1.14,1.02,1.29) increased risk of CHD, respectively. Further regression analyses confirmed that the identified metabolites and the four PCs were positively associated with TG and ALT. Interestingly, glycolic acid was negatively associated with sleep quality and PSQI. Participants with night sleep mode tended to have a high level of the identified lipids, especially FFA (20:4).

CONCLUSION

In the present pilot study, our findings provide clues on alterations of lipid and energy metabolism in CHD patients without traditional risk factors, with multiple triacylglycerols and diacylglycerols metabolites seemingly elevated and certain nonlipids metabolites (e.g., succinic acid and glycolic acid) decreased in cases. Considering the limit sample size, further studies are warranted to confirm our results.

摘要

目的

脂质、能量代谢改变及睡眠障碍与冠心病(CHD)相关,但非阻塞性冠状动脉粥样硬化性冠心病的代谢特征和睡眠节律尚不清楚。本初步研究旨在调查无传统危险因素的冠心病患者的脂质组和中心碳代谢物谱以及相关睡眠特征。

方法

2021年1月至7月,从上海中山医院心内科随机选取15例冠心病患者和15例健康对照。对血浆中的464种脂质和45种中心碳代谢物(CCM)进行定量分析。通过正交投影到潜在结构判别分析(OPLS-DA)选择代谢特征,并进行主成分分析(PCA),以将已鉴定代谢物的谱与冠心病风险、睡眠模式、心脏代谢特征和心脏电生理参数联系起来。

结果

使用OPLS-DA,我们鉴定出40种在冠心病患者中发生改变的代谢物(投影变量影响>1),其中38种脂质升高,包括25种三酰甘油(TAGs)、8种二酰甘油(DAGs),2种CCM代谢物(即琥珀酸和乙醇酸)降低。使用PCA,确定了四个主成分(PCs),并与冠心病风险增加相关。具体而言,以高水平DAG(18:1)、低琥珀酸为特征的PC增加一个标准单位,以及以高水平两种鞘磷脂[SM(26:0)和SM(24:0)]为特征的PC增加一个标准单位,分别与冠心病风险增加21%[优势比(OR)=1.21,95%CI:1.02,1.43]和14%(OR=1.14,1.02,1.29)相关。进一步的回归分析证实,已鉴定的代谢物和四个PCs与甘油三酯(TG)和谷丙转氨酶(ALT)呈正相关。有趣的是,乙醇酸与睡眠质量和匹兹堡睡眠质量指数(PSQI)呈负相关。夜间睡眠模式的参与者往往具有高水平的已鉴定脂质,尤其是游离脂肪酸(FFA,20:4)。

结论

在本初步研究中,我们的发现为无传统危险因素的冠心病患者脂质和能量代谢改变提供了线索,病例中多种三酰甘油和二酰甘油代谢物似乎升高,某些非脂质代谢物(如琥珀酸和乙醇酸)降低。考虑到样本量有限,需要进一步研究来证实我们的结果。

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