Serum metabolic profile in acute myocardial infarction mice model: An LC-MS/MS-based targeted metabolomic analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

XUN Siqi ^1,2 , GAN Changping ^1,2 , GUO Yingqiang ^1,2 ,  QIN Chaoyi ^1,2

1. Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;
2. Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;

Corresponding author：

QIN Chaoyi, Email: qinchaoyi@wchscu.cn

Keywords：

Metabolomics; myocardial infarction; serine

DOI：

10.7507/1007-4848.202302079

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To analyze the metabolic characteristics of myocardial infarction (MI) using metabolomics to better understand its pathogenesis and to explore new therapeutic directions for MI. Methods Serum metabolites in ten acute MI mice and five sham-control mice were analyzed by UHPLC-QqQ/MS, and SPSS was used for statistical analysis. MetaboAnalyst 5.0 was used to analyze the metabolic pathways of the differential metabolites and build a metabolic network. Results One hundred and twenty-nine metabolites were detected by UHPLC-QqQ/MS. Significant serum metabolite differences were found between MI mice and normal controls. Fifty out of 129 metabolites in serum were associated with MI. In addition, the most important metabolic pathways were D-glutamate metabolism, alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate acid metabolism. Conclusion Metabolites in serine-related metabolic pathways reduce in serum in MI. We propose a new therapeutic direction for myocardial protection in MI.

Citation： XUN Siqi, GAN Changping, GUO Yingqiang, QIN Chaoyi. Serum metabolic profile in acute myocardial infarction mice model: An LC-MS/MS-based targeted metabolomic analysis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(11): 1609-1617. doi: 10.7507/1007-4848.202302079 Copy

1.	Jannesar K, Abbaszadeh S, Malekinejad H, et al. Cardioprotective effects of memantine in myocardial ischemia: Ex vivo and in vivo studies. Eur J Pharmacol, 2020, 882: 173277.
2.	Gao M, Yin D, Chen J, et al. Activating the interleukin-6-Gp130-STAT3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleus. BMC Cardiovasc Disord, 2020, 20(1): 60.
3.	Xie H, Zha E, Zhang Y. Identification of featured metabolism-related genes in patients with acute myocardial infarction. Dis Markers, 2020, 2020: 8880004.
4.	Wang XX, Wang D, Wu JY, et al. Metabolic Characterization of myocardial infarction using GC-MS-based tissue metabolomics. Int Heart J, 2017, 58(3): 441-446.
5.	Liu W, Shen J, Li Y, et al. Pyroptosis inhibition improves the symptom of acute myocardial infarction. Cell Death Dis, 2021, 12(10): 852.
6.	Saito Y, Oyama K, Tsujita K, et al. Treatment strategies of acute myocardial infarction: Updates on revascularization, pharmacological therapy, and beyond. J Cardiol, 2023, 81(2): 168-178.
7.	Jankowski P, Topor-Madry R, Gasior M, et al. Innovative managed care may be related to improved prognosis for acute myocardial infarction survivors. Circ Cardiovasc Qual Outcomes, 2021, 14(8): e007800.
8.	Dauerman HL, Ibanez B. The edge of time in acute myocardial infarction. J Am Coll Cardiol, 2021, 77(15): 1871-1874.
9.	Damluji AA, van Diepen S, Katz JN, et al. Mechanical complications of acute myocardial infarction: A scientific statement from the American Heart Association. Circulation, 2021, 144(2): e16-e35.
10.	Wang XD, Kang S. Ferroptosis in myocardial infarction: Not a marker but a maker. Open Biol, 2021, 11(4): 200367.
11.	Berg M, Vanaerschot M, Jankevics A, et al. LC-MS metabolomics from study design to data-analysis - using a versatile pathogen as a test case. Comput Struct Biotechnol J, 2013, 4: e201301002.
12.	Meng X, Pang H, Sun F, et al. Simultaneous 3-nitrophenylhydrazine derivatization strategy of carbonyl, carboxyl and phosphoryl submetabolome for LC-MS/MS-based targeted metabolomics with improved sensitivity and coverage. Anal Chem, 2021, 93(29): 10075-10083.
13.	Liu W, Zhang L, Shi X, et al. Cross-comparative metabolomics reveal sex-age specific metabolic fingerprints and metabolic interactions in acute myocardial infarction. Free Radic Biol Med, 2022, 183: 25-34.
14.	Deng D, Liu L, Xu G, et al. Epidemiology and serum metabolic characteristics of acute myocardial infarction patients in chest pain centers. Iran J Public Health, 2018, 47(7): 1017-1029.
15.	Lindsey ML, Brunt KR, Kirk JA, et al. Guidelines for in vivo mouse models of myocardial infarction. Am J Physiol Heart Circ Physiol, 2021, 321(6): H1056-H1073.
16.	Anwar MA, Ford WR, Herbert AA, et al. Signal transduction and modulating pathways in tryptamine-evoked vasopressor responses of the rat isolated perfused mesenteric bed. Vascul Pharmacol, 2013, 58(1-2): 140-149.
17.	Shi M, Wang C, Mei H, et al. Genetic architecture of plasma alpha-aminoadipic acid reveals a relationship with high-density lipoprotein cholesterol. J Am Heart Assoc, 2022, 11(11): e024388.
18.	Matthews DE. Review of lysine metabolism with a focus on humans. J Nutr, 2020, 150(Suppl 1): 2548S-2555S.
19.	Coyle JT, Balu D, Wolosker H. D-serine, the shape-shifting NMDA receptor co-agonist. Neurochem Res, 2020, 45(6): 1344-1353.
20.	Shad KF, Luqman N, Simpson AM, et al. Peripheral biomarker for vascular disorders. Biomark Insights, 2018, 13: 1177271918812467.
21.	Andersson C, Liu C, Cheng S, et al. Metabolomic signatures of cardiac remodelling and heart failure risk in the community. ESC Heart Fail, 2020, 7(6): 3707-3715.
22.	Zhou Y, Zhang X, Chen R, et al. Serum amino acid metabolic profiles of ankylosing spondylitis by targeted metabolomics analysis. Clin Rheumatol, 2020, 39(8): 2325-2336.
23.	Perea-Gil I, Seeger T, Bruyneel AAN, et al. Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy. Eur Heart J, 2022, 43(36): 3477-3489.
24.	Hogewind-Schoonenboom JE, Huang L, de Groof F, et al. Threonine requirement of the enterally fed term infant in the first month of life. J Pediatr Gastroenterol Nutr, 2015, 61(3): 373-379.
25.	Leibovitzh H, Lee SH, Xue M, et al. Altered gut microbiome composition and function are associated with gut barrier dysfunction in healthy relatives of patients with crohn's disease. Gastroenterology, 2022, 163(5): 1364-1376.
26.	Tang Q, Tan P, Ma N, et al. Physiological functions of threonine in animals: Beyond nutrition metabolism. Nutrients, 2021, 13(8): 2592.
27.	Kolwicz SC, Jr. , Purohit S, Tian R. Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ Res, 2013, 113(5): 603-616.
28.	Lai Q, Yuan GY, Wang H, et al. Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies. Acta Pharmacol Sin, 2020, 41(8): 1058-1072.
29.	Lai Q, Yuan G, Wang H, et al. Metabolomic profiling of metoprolol-induced cardioprotection in a murine model of acute myocardial ischemia. Biomed Pharmacother, 2020, 124: 109820.
30.	Liu B, el Alaoui-Talibi Z, Clanachan AS, et al. Uncoupling of contractile function from mitochondrial TCA cycle activity and MVO₂ during reperfusion of ischemic hearts. Am J Physiol, 1996, 270(1 Pt 2): H72-H80.
31.	Fang M, Meng Y, Du Z, et al. The synergistic mechanism of total saponins and flavonoids in notoginseng-safflower against myocardial infarction using a comprehensive metabolomics strategy. Molecules, 2022, 27(24): 8860.
32.	Ding Y, Pedersen ER, Svingen GF, et al. Methylenetetrahydrofolate dehydrogenase 1 polymorphisms modify the associations of plasma glycine and serine with risk of acute myocardial infarction in patients with stable angina pectoris in WENBIT (Western Norway B Vitamin Intervention Trial). Circ Cardiovasc Genet, 2016, 9(6): 541-547.
33.	Padron-Barthe L, Villalba-Orero M, Gomez-Salinero JM, et al. Activation of serine one-carbon metabolism by calcineurin abeta1 reduces myocardial hypertrophy and improves ventricular function. J Am Coll Cardiol, 2018, 71(6): 654-667.
34.	Pan S, Fan M, Liu Z, et al. Serine, glycine and one-carbon metabolism in cancer (Review). Int J Oncol, 2021, 58(2): 158-170.
35.	Maynard AG, Kanarek N. NADH ties one-carbon metabolism to cellular respiration. Cell Metab, 2020, 31(4): 660-662.
36.	Murashige D, Jang C, Neinast M, et al. Comprehensive quantification of fuel use by the failing and nonfailing human heart. Science, 2020, 370(6514): 364-368.

1. Jannesar K, Abbaszadeh S, Malekinejad H, et al. Cardioprotective effects of memantine in myocardial ischemia: Ex vivo and in vivo studies. Eur J Pharmacol, 2020, 882: 173277.
2. Gao M, Yin D, Chen J, et al. Activating the interleukin-6-Gp130-STAT3 pathway ameliorates ventricular electrical stability in myocardial infarction rats by modulating neurotransmitters in the paraventricular nucleus. BMC Cardiovasc Disord, 2020, 20(1): 60.
3. Xie H, Zha E, Zhang Y. Identification of featured metabolism-related genes in patients with acute myocardial infarction. Dis Markers, 2020, 2020: 8880004.
4. Wang XX, Wang D, Wu JY, et al. Metabolic Characterization of myocardial infarction using GC-MS-based tissue metabolomics. Int Heart J, 2017, 58(3): 441-446.
5. Liu W, Shen J, Li Y, et al. Pyroptosis inhibition improves the symptom of acute myocardial infarction. Cell Death Dis, 2021, 12(10): 852.
6. Saito Y, Oyama K, Tsujita K, et al. Treatment strategies of acute myocardial infarction: Updates on revascularization, pharmacological therapy, and beyond. J Cardiol, 2023, 81(2): 168-178.
7. Jankowski P, Topor-Madry R, Gasior M, et al. Innovative managed care may be related to improved prognosis for acute myocardial infarction survivors. Circ Cardiovasc Qual Outcomes, 2021, 14(8): e007800.
8. Dauerman HL, Ibanez B. The edge of time in acute myocardial infarction. J Am Coll Cardiol, 2021, 77(15): 1871-1874.
9. Damluji AA, van Diepen S, Katz JN, et al. Mechanical complications of acute myocardial infarction: A scientific statement from the American Heart Association. Circulation, 2021, 144(2): e16-e35.
10. Wang XD, Kang S. Ferroptosis in myocardial infarction: Not a marker but a maker. Open Biol, 2021, 11(4): 200367.
11. Berg M, Vanaerschot M, Jankevics A, et al. LC-MS metabolomics from study design to data-analysis - using a versatile pathogen as a test case. Comput Struct Biotechnol J, 2013, 4: e201301002.
12. Meng X, Pang H, Sun F, et al. Simultaneous 3-nitrophenylhydrazine derivatization strategy of carbonyl, carboxyl and phosphoryl submetabolome for LC-MS/MS-based targeted metabolomics with improved sensitivity and coverage. Anal Chem, 2021, 93(29): 10075-10083.
13. Liu W, Zhang L, Shi X, et al. Cross-comparative metabolomics reveal sex-age specific metabolic fingerprints and metabolic interactions in acute myocardial infarction. Free Radic Biol Med, 2022, 183: 25-34.
14. Deng D, Liu L, Xu G, et al. Epidemiology and serum metabolic characteristics of acute myocardial infarction patients in chest pain centers. Iran J Public Health, 2018, 47(7): 1017-1029.
15. Lindsey ML, Brunt KR, Kirk JA, et al. Guidelines for in vivo mouse models of myocardial infarction. Am J Physiol Heart Circ Physiol, 2021, 321(6): H1056-H1073.
16. Anwar MA, Ford WR, Herbert AA, et al. Signal transduction and modulating pathways in tryptamine-evoked vasopressor responses of the rat isolated perfused mesenteric bed. Vascul Pharmacol, 2013, 58(1-2): 140-149.
17. Shi M, Wang C, Mei H, et al. Genetic architecture of plasma alpha-aminoadipic acid reveals a relationship with high-density lipoprotein cholesterol. J Am Heart Assoc, 2022, 11(11): e024388.
18. Matthews DE. Review of lysine metabolism with a focus on humans. J Nutr, 2020, 150(Suppl 1): 2548S-2555S.
19. Coyle JT, Balu D, Wolosker H. D-serine, the shape-shifting NMDA receptor co-agonist. Neurochem Res, 2020, 45(6): 1344-1353.
20. Shad KF, Luqman N, Simpson AM, et al. Peripheral biomarker for vascular disorders. Biomark Insights, 2018, 13: 1177271918812467.
21. Andersson C, Liu C, Cheng S, et al. Metabolomic signatures of cardiac remodelling and heart failure risk in the community. ESC Heart Fail, 2020, 7(6): 3707-3715.
22. Zhou Y, Zhang X, Chen R, et al. Serum amino acid metabolic profiles of ankylosing spondylitis by targeted metabolomics analysis. Clin Rheumatol, 2020, 39(8): 2325-2336.
23. Perea-Gil I, Seeger T, Bruyneel AAN, et al. Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy. Eur Heart J, 2022, 43(36): 3477-3489.
24. Hogewind-Schoonenboom JE, Huang L, de Groof F, et al. Threonine requirement of the enterally fed term infant in the first month of life. J Pediatr Gastroenterol Nutr, 2015, 61(3): 373-379.
25. Leibovitzh H, Lee SH, Xue M, et al. Altered gut microbiome composition and function are associated with gut barrier dysfunction in healthy relatives of patients with crohn's disease. Gastroenterology, 2022, 163(5): 1364-1376.
26. Tang Q, Tan P, Ma N, et al. Physiological functions of threonine in animals: Beyond nutrition metabolism. Nutrients, 2021, 13(8): 2592.
27. Kolwicz SC, Jr. , Purohit S, Tian R. Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ Res, 2013, 113(5): 603-616.
28. Lai Q, Yuan GY, Wang H, et al. Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies. Acta Pharmacol Sin, 2020, 41(8): 1058-1072.
29. Lai Q, Yuan G, Wang H, et al. Metabolomic profiling of metoprolol-induced cardioprotection in a murine model of acute myocardial ischemia. Biomed Pharmacother, 2020, 124: 109820.
30. Liu B, el Alaoui-Talibi Z, Clanachan AS, et al. Uncoupling of contractile function from mitochondrial TCA cycle activity and MVO₂ during reperfusion of ischemic hearts. Am J Physiol, 1996, 270(1 Pt 2): H72-H80.
31. Fang M, Meng Y, Du Z, et al. The synergistic mechanism of total saponins and flavonoids in notoginseng-safflower against myocardial infarction using a comprehensive metabolomics strategy. Molecules, 2022, 27(24): 8860.
32. Ding Y, Pedersen ER, Svingen GF, et al. Methylenetetrahydrofolate dehydrogenase 1 polymorphisms modify the associations of plasma glycine and serine with risk of acute myocardial infarction in patients with stable angina pectoris in WENBIT (Western Norway B Vitamin Intervention Trial). Circ Cardiovasc Genet, 2016, 9(6): 541-547.
33. Padron-Barthe L, Villalba-Orero M, Gomez-Salinero JM, et al. Activation of serine one-carbon metabolism by calcineurin abeta1 reduces myocardial hypertrophy and improves ventricular function. J Am Coll Cardiol, 2018, 71(6): 654-667.
34. Pan S, Fan M, Liu Z, et al. Serine, glycine and one-carbon metabolism in cancer (Review). Int J Oncol, 2021, 58(2): 158-170.
35. Maynard AG, Kanarek N. NADH ties one-carbon metabolism to cellular respiration. Cell Metab, 2020, 31(4): 660-662.
36. Murashige D, Jang C, Neinast M, et al. Comprehensive quantification of fuel use by the failing and nonfailing human heart. Science, 2020, 370(6514): 364-368.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Serum metabolic profile in acute myocardial infarction mice model: An LC-MS/MS-based targeted metabolomic analysis

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content