Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (Y.S., R.Z., L.T., Z.H., J.F., J.C., W.C., L.B., J.H., J.D.B., C.L.).
Division of Nephrology, Department of Medicine, College of Medicine, University of Illinois at Chicago (Y.P., X.S., T.N.K.).
Hypertension. 2024 Sep;81(9):1966-1975. doi: 10.1161/HYPERTENSIONAHA.124.22999. Epub 2024 Jul 15.
The blood pressure (BP) etiologic study is complex due to multifactorial influences, including genetic, environmental, lifestyle, and their intricate interplays. We used a metabolomics approach to capture internal pathways and external exposures and to study BP regulation mechanisms after well-controlled dietary interventions.
In the ProBP trail (Protein and Blood Pressure), a double-blinded crossover randomized controlled trial, participants underwent dietary interventions of carbohydrate, soy protein, and milk protein, receiving 40 g daily for 8 weeks, with 3-week washout periods. We measured plasma samples collected at baseline and at the end of each dietary intervention. Multivariate linear models were used to evaluate the association between metabolites and systolic/diastolic BP. Nominally significant metabolites were examined for enriching biological pathways. Significant ProBP findings were evaluated for replication among 1311 participants of the BHS (Bogalusa Heart Study), a population-based study conducted in the same area as ProBP.
After Bonferroni correction for 77 independent metabolite clusters (α=6.49×10), 18 metabolites were significantly associated with BP at baseline or the end of a dietary intervention, of which 11 were replicated in BHS. Seven emerged as novel discoveries, which are as follows: 1-linoleoyl-GPE (18:2), 1-oleoyl-GPE (18:1), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2), 1-palmitoyl-2-oleoyl-GPE (16:0/18:1), maltose, N-stearoyl-sphinganine (d18:0/18:0), and N6-carbamoylthreonyladenosine. Pathway enrichment analyses suggested dietary protein intervention might reduce BP through pathways related to G protein-coupled receptors, incretin function, selenium micronutrient network, and mitochondrial biogenesis.
Seven novel metabolites were identified to be associated with BP at the end of different dietary interventions. The beneficial effects of protein interventions might be mediated through specific metabolic pathways.
由于遗传、环境、生活方式等多种因素的影响，血压（BP）病因学研究非常复杂，且这些因素之间存在错综复杂的相互作用。我们采用代谢组学方法来捕捉内部途径和外部暴露，并在经过严格控制的饮食干预后研究 BP 调节机制。
在 ProBP 试验（蛋白质与血压）中，我们采用了一项双盲交叉随机对照试验，参与者接受了碳水化合物、大豆蛋白和牛奶蛋白的饮食干预，每天摄入 40 克，持续 8 周，期间有 3 周的洗脱期。我们测量了基线和每个饮食干预结束时采集的血浆样本。采用多元线性模型评估代谢物与收缩压/舒张压之间的关联。对具有显著统计学意义的代谢物进行生物途径富集分析。对 ProBP 中发现的有统计学意义的结果，在同一地区开展的人群为基础的 Bogalusa 心脏研究（BHS）中 1311 名参与者中进行了复制。
在对 77 个独立代谢物簇（α=6.49×10）进行 Bonferroni 校正后，有 18 种代谢物与基线或饮食干预结束时的 BP 显著相关，其中 11 种在 BHS 中得到复制。有 7 种代谢物是新发现，分别为：1-亚油酸-GPE（18:2）、1-油酸-GPE（18:1）、1-硬脂酰-2-亚油酰-GPC（18:0/18:2）、1-棕榈酰-2-油酰-GPE（16:0/18:1）、麦芽糖、N-硬脂酰鞘氨醇（d18:0/18:0）和 N6-氨甲酰基苏氨酸腺苷。途径富集分析表明，饮食蛋白干预可能通过与 G 蛋白偶联受体、肠降血糖素功能、硒微量营养素网络和线粒体生物发生相关的途径降低 BP。
确定了 7 种新的代谢物与不同饮食干预结束时的 BP 相关。蛋白干预的有益效果可能是通过特定的代谢途径介导的。
