Zhang Z Y, Feng X Y, Wang Z H, Huang Y Z, Yang W B, Zhang W J, Zhou J, Yuan Z Y
Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2023 Jul 24;51(7):722-730. doi: 10.3760/cma.j.cn112148-20230329-00182.
To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and <0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.
利用代谢组学揭示射血分数保留的心力衰竭（HFpEF）小鼠和射血分数降低的心力衰竭（HFrEF）小鼠心肌代谢特征的异同。将实验小鼠分为4组，包括对照组、HFpEF组、假手术组和HFrEF组（每组10只小鼠）。采用高脂饮食和盐酸Nω-硝基精氨酸甲酯（L-NAME）构建“双打击”HFpEF小鼠模型。采用横向主动脉缩窄（TAC）手术构建HFrEF小鼠模型。通过非靶向代谢组学（UHPLC-QE-MS）检测HFpEF和HFrEF小鼠心肌中代谢物的差异表达。以投影变量重要性>1且<0.05作为筛选和分类小鼠模型间差异表达代谢物的标准。KEGG功能富集和通路影响分析表明，HFpEF和HFrEF小鼠的代谢通路均有显著改变。在HFpEF小鼠中检测到109种差异表达代谢物，在HFrEF小鼠中检测到270种差异表达代谢物。与对照组相比，HFpEF小鼠中变化最显著的代谢物是甘油磷脂，而HFrEF小鼠中羧酸及其衍生物的比例最大。KEGG富集和通路影响分析表明，HFpEF小鼠中差异表达的代谢物主要富集在不饱和脂肪酸生物合成、醚脂代谢、氨基糖和核苷酸糖代谢、甘油磷脂代谢、花生四烯酸代谢以及精氨酸和脯氨酸代谢等通路中。HFrEF小鼠中差异表达的代谢物主要富集在精氨酸和脯氨酸代谢、甘氨酸、丝氨酸和苏氨酸代谢、泛酸和辅酶A生物合成、甘油磷脂代谢、烟酸和烟酰胺代谢以及花生四烯酸代谢等通路中。与HFrEF小鼠相比，HFpEF小鼠的心肌代谢物表达谱有显著差异。此外，HFpEF和HFrEF小鼠的不饱和脂肪酸生物合成、花生四烯酸代谢、甘油磷脂代谢以及精氨酸和脯氨酸代谢均有显著改变，提示这些代谢通路可能在两种类型心力衰竭的疾病进展中起重要作用。
