Shen Yang, Wang Pan, Yang Xinchun, Chen Mulei, Dong Ying, Li Jing
Department of Nephrology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Heart Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Front Cardiovasc Med. 2023 May 4;10:1102754. doi: 10.3389/fcvm.2023.1102754. eCollection 2023.
It has been well acknowledged that disordered intestinal microflora and their fermented products play crucial role during the development of hypertension (HTN). Aberrant profiles of fecal bacteria have been documented in subjects with isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) previously. Nevertheless, evidence regarding the association of metabolic products in the bloodstream with ISH, IDH and combined systolic and diastolic HTN (SDH) remains scarce.
We performed a cross-sectional study and conducted untargeted liquid chromatography-mass spectrometry (LC/MS) analysis on serum samples of 119 participants, including 13 subjects with normotension (SBP < 120/DBP < 80 mm Hg), 11 individuals with ISH (SBP ≥ 130/DBP < 80 mm Hg), 27 patients with IDH (SBP < 130/DBP ≥ 80 mm Hg), and 68 SDH patients (SBP ≥ 130, DBP ≥ 80 mm Hg).
Here, the results showed clearly separated clusters in PLS-DA and OPLS-DA score plots for patients suffering from ISH, IDH and SDH when compared with normotension controls. The ISH group was characterized by elevated levels of 3,5-tetradecadien carnitine and notable reduction of maleic acid. While IDH patients were enriched with metabolites in L-lactic acid and depleted in citric acid. Stearoylcarnitine was identified to be specifically enriched in SDH group. The differentially abundant metabolites between ISH and controls were involved in tyrosine metabolism pathways, and in biosynthesis of phenylalanine for those between SDH and controls. Potential linkages between the gut microbial and serum metabolic signatures were detected within ISH, IDH and SDH groups. Furthermore, we found the association of discriminatory metabolites with the characteristics of patients.
Our findings demonstrate disparate blood metabolomics signatures across ISH, IDH and SDH, with differentially enriched metabolites and potential functional pathways identified, reveal the underlying microbiome and metabolome network in HTN subtypes, and provide potential targets for disease classification and therapeutic strategy in clinical practice.
肠道微生物群紊乱及其发酵产物在高血压（HTN）的发生发展过程中起着关键作用，这一点已得到广泛认可。先前已有文献报道，单纯收缩期高血压（ISH）和单纯舒张期高血压（IDH）患者的粪便细菌谱异常。然而，关于血液中代谢产物与ISH、IDH及收缩压和舒张压联合高血压（SDH）之间关联的证据仍然匮乏。
我们进行了一项横断面研究，对119名参与者的血清样本进行了非靶向液相色谱 - 质谱（LC/MS）分析，其中包括13名血压正常者（收缩压<120/舒张压<80 mmHg）、11名ISH患者（收缩压≥130/舒张压<80 mmHg）、27名IDH患者（收缩压<130/舒张压≥80 mmHg）以及68名SDH患者（收缩压≥130，舒张压≥80 mmHg）。
在此，结果显示，与血压正常对照组相比，ISH、IDH和SDH患者在偏最小二乘法判别分析（PLS - DA）和正交偏最小二乘法判别分析（OPLS - DA）得分图中呈现出明显分离的聚类。ISH组的特征是3,5 - 十四碳二烯肉碱水平升高，马来酸显著降低。而IDH患者的L - 乳酸代谢产物丰富，柠檬酸代谢产物减少。硬脂酰肉碱被确定在SDH组中特异性富集。ISH与对照组之间差异丰富的代谢产物参与酪氨酸代谢途径，SDH与对照组之间差异丰富的代谢产物参与苯丙氨酸生物合成途径。在ISH、IDH和SDH组中检测到肠道微生物与血清代谢特征之间的潜在联系。此外，我们发现了鉴别性代谢产物与患者特征之间的关联。
我们的研究结果表明，ISH、IDH和SDH的血液代谢组学特征存在差异，鉴定出了差异富集的代谢产物和潜在的功能途径，揭示了高血压亚型潜在的微生物组和代谢组网络，并为临床实践中的疾病分类和治疗策略提供了潜在靶点。
