Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
J Pharm Biomed Anal. 2021 Nov 30;206:114381. doi: 10.1016/j.jpba.2021.114381. Epub 2021 Sep 20.
Coronary heart disease (CHD) is a multifactorial disease associated with complicated altered metabolic pathways, especially when it occurs with type 2 diabetes (T2D). Identification of metabolic changes could provide further understanding of the underlying pathological link between with CHD and T2D. In this study, 61 controls, 30 consecutive patients with only T2D, 188 with confirmed CHD among which 50 also having T2D were enrolled. Quantitative H nuclear magnetic resonance (H NMR) based metabonomic approach was used to obtain the plasma metabolic profiles of the study samples. Multivariate principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to evaluate the differences of metabolites. Compared with controls, there were significant differences in CHD patient with T2D groups including BCAAs (isoleucine, leucine, and valine) and phenylalanine by using quantitative metabolomic profiling (all p < 0.05). With OPLS-DA, the results showed that, compared to CHD patients without T2D, there had higher levels of metabolites for leucine, valine, fumarate, tyrosine, and phenylalanine in the plasma of CHD patients with T2D. Moreover, the CHD patients with T2D showed modified phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis and degradation compared with CHD patients without T2D. By H NMR based quantitative metabolomic method, our findings suggest that T2D has important effects on BCAAs and AAAs metabolism in CHD patients indicating altered cardiac energy metabolism and activated signaling pathway could be potential targets for therapy in CHD disease combined with T2D.
冠心病(CHD)是一种与复杂代谢途径改变相关的多因素疾病,尤其是在伴有 2 型糖尿病(T2D)时。代谢变化的鉴定可以进一步了解 CHD 和 T2D 之间潜在的病理联系。在这项研究中,纳入了 61 名对照者、30 名单纯 T2D 连续患者、188 名确诊 CHD 患者,其中 50 名也患有 T2D。采用基于定量 H 核磁共振(H NMR)的代谢组学方法获取研究样本的血浆代谢谱。采用多元主成分分析和正交偏最小二乘判别分析(OPLS-DA)评估代谢物的差异。与对照组相比,T2D 组的 CHD 患者存在显著差异,包括支链氨基酸(异亮氨酸、亮氨酸和缬氨酸)和苯丙氨酸(p 值均<0.05)。通过 OPLS-DA 分析,与无 T2D 的 CHD 患者相比,T2D 的 CHD 患者血浆中亮氨酸、缬氨酸、富马酸、酪氨酸和苯丙氨酸的水平更高。此外,与无 T2D 的 CHD 患者相比,T2D 的 CHD 患者的苯丙氨酸、酪氨酸和色氨酸生物合成、亮氨酸、缬氨酸和异亮氨酸生物合成和降解途径发生了改变。通过基于 H NMR 的定量代谢组学方法,我们的研究结果表明,T2D 对 CHD 患者的支链氨基酸和芳香族氨基酸代谢有重要影响,表明改变的心脏能量代谢和激活的信号通路可能是合并 T2D 的 CHD 疾病治疗的潜在靶点。