Liu Langsha, Luo Fanyan
Department of Cardiac Surgery, Xiangya Hospital, Central South University, 410008 Changsha, Hunan, China.
Front Biosci (Landmark Ed). 2022 Mar 16;27(3):100. doi: 10.31083/j.fbl2703100.
Unstable angina pectoris (UAP) is a type of Coronary artery disease (CAD) characterized by a series of angina symptoms. Insulin-like growth factor 1 (IGF-1) system may be related to CAD. However, the correlation between the IGF-1 system, metabolism, and gut microbiota has not been studied. In the present study, we investigated the alterations of serum IGF-1 system, metabolomics, and gut microbiota in patients with UAP.
Serum and stool samples from healthy volunteers and UAP patients were collected. Serum metabolomics, PAPP-A, IGF-1, IGFBP-4, STC2, hs-CRP, TNF-α, and IL-6 were detected in serum samples by LC-MS, and commercial ELISA kits, respectively. Fecal short-chain fatty acids (SCFAs) were measured by gas chromatography. 16S rDNA was used to measure the changes of the gut microbiota. The correlation of the above indicators was analyzed.
There were 24 upregulated and 31 downregulated metabolites in the serum of UAP patients compared to those in the controls. Pathway analysis showed that these metabolites were enriched in pathways including linoleic acid metabolism, amino acid metabolism, starch metabolism, sucrose metabolism, and citrate cycle (TCA cycle), . Additionally, the UAP patients had lower fecal levels of 2-hydroxyisobutyric acid and succinic acid. 16S rDNA sequencing results showed that the relative abundances of , , , , Synergistaceae, and were significantly higher in the UAP patients than the healthy subjects. Moreover, the UAP patients had lower serum IGF-1, IGFBP-4, and STC2 and higher serum inflammatory cytokines (hs-CRP, TNF-α, and IL-6) levels than the healthy controls. Furthermore, there was a strong correlation between serum amino acids and IL-6, which played an important role in the development of UAP.
These results indicated that the UAP patients had decreased serum IGF-1 level and imbalanced amino acids metabolism, which may be caused by the altered gut microbiota. It may provide a new therapeutic strategy for unstable angina pectoris.
不稳定型心绞痛（UAP）是一种以一系列心绞痛症状为特征的冠状动脉疾病（CAD）。胰岛素样生长因子1（IGF-1）系统可能与CAD相关。然而，IGF-1系统、代谢和肠道微生物群之间的相关性尚未得到研究。在本研究中，我们调查了UAP患者血清IGF-1系统、代谢组学和肠道微生物群的变化。
收集健康志愿者和UAP患者的血清和粪便样本。分别通过液相色谱-质谱联用（LC-MS）和商用酶联免疫吸附测定（ELISA）试剂盒检测血清样本中的血清代谢组学、妊娠相关血浆蛋白-A（PAPP-A）、IGF-1、胰岛素样生长因子结合蛋白4（IGFBP-4）、基质细胞衍生因子2（STC2）、高敏C反应蛋白（hs-CRP）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）。通过气相色谱法测量粪便短链脂肪酸（SCFA）。采用16S核糖体DNA（rDNA）检测肠道微生物群的变化。分析上述指标之间的相关性。
与对照组相比，UAP患者血清中有24种代谢物上调，31种代谢物下调。通路分析表明，这些代谢物在包括亚油酸代谢、氨基酸代谢、淀粉代谢、蔗糖代谢和柠檬酸循环（三羧酸循环）等通路中富集。此外，UAP患者粪便中2-羟基异丁酸和琥珀酸水平较低。16S rDNA测序结果显示，UAP患者中普雷沃菌属、拟杆菌属、双歧杆菌属、粪杆菌属、协同杆菌科和瘤胃球菌属的相对丰度显著高于健康受试者。此外，与健康对照组相比，UAP患者血清IGF-1、IGFBP-4和STC2水平较低，血清炎症细胞因子（hs-CRP、TNF-α和IL-6）水平较高。此外，血清氨基酸与IL-6之间存在强相关性，IL-6在UAP的发生发展中起重要作用。
这些结果表明，UAP患者血清IGF-1水平降低，氨基酸代谢失衡，这可能是由肠道微生物群改变引起的。这可能为不稳定型心绞痛提供一种新的治疗策略。
