Graduate Institute of Clinical Medicine, College of Medicines, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Nutrients. 2019 Dec 12;11(12):3033. doi: 10.3390/nu11123033.
Short-chain fatty acids (SCFAs) can reduce pro-inflammatory parameters and oxidative stress, providing potential cardiovascular (CV) benefits. Although some evidence links SCFAs with host metabolic health via several biological mechanisms, the role of SCFA on CV disease in patients with kidney disease remains unclear. Herein, we investigate the association between a SCFA, 2-methylbutyric acid, and target CV proteomics to explore the potential pathophysiology of SCFA-related CV benefit in patients with kidney disease. Circulating 2-methylbutyric acid was quantified by high-performance liquid chromatography and 181 CV proteins by a proximity extension assay in 163 patients undergoing hemodialysis (HD). The associations between 2-methylbutyric acid and CV proteins were evaluated using linear regression analysis with age and gender, and multiple testing adjustment. The selected CV protein in the discovery phase was further confirmed in multivariable-adjusted models and evaluated by continuous scale association. The mean value of circulating 2-methylbutyric acid was 0.22 ± 0.02 µM, which was negatively associated with bone morphogenetic protein 6 (BMP-6) according to the false discovery rate (FDR) multiple testing adjustment method. The 2-methylbutyric acid level remained negatively associated with BMP-6 (β coefficient -1.00, 95% confidence interval -1.45 to -0.55, < 0.001) after controlling for other CV risk factors in multivariable models. The cubic spline curve demonstrated a linear relationship. In conclusion, circulating 2-methylbutyric acid level was negatively associated with BMP-6, suggesting that this pathway maybe involved in vascular health in patients undergoing HD. However, further in vitro work is still needed to validate the translation of the mechanistic pathways.
短链脂肪酸（SCFAs）可以降低促炎参数和氧化应激，提供潜在的心血管（CV）益处。尽管一些证据通过几种生物学机制将 SCFA 与宿主代谢健康联系起来，但 SCFA 对肾病患者 CV 疾病的作用仍不清楚。在此，我们研究了一种 SCFA，2-甲基丁酸，与目标 CV 蛋白质组学之间的关联，以探索 SCFA 相关 CV 益处与肾病患者潜在病理生理学之间的关系。通过高效液相色谱法测定 163 名接受血液透析（HD）的患者的循环 2-甲基丁酸，通过接近延伸测定法测定 181 种 CV 蛋白。使用线性回归分析评估 2-甲基丁酸与 CV 蛋白之间的关联，包括年龄和性别，并进行多次测试调整。在发现阶段选择的 CV 蛋白在多变量调整模型中进一步确认，并通过连续尺度关联进行评估。循环 2-甲基丁酸的平均值为 0.22 ± 0.02 µM，根据错误发现率（FDR）多重测试调整方法，其与骨形态发生蛋白 6（BMP-6）呈负相关。在多变量模型中控制其他 CV 危险因素后，2-甲基丁酸水平仍与 BMP-6 呈负相关（β系数-1.00，95%置信区间-1.45 至-0.55，<0.001）。三次样条曲线显示出线性关系。总之，循环 2-甲基丁酸水平与 BMP-6 呈负相关，表明该途径可能与接受 HD 的患者的血管健康有关。然而，仍需要进一步的体外工作来验证机制途径的转化。
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