Characteristics of plasma lipid metabolism and potential biomarkers in patients with acute myocardial infarction

Wenxin RU; Han HU; Ting ZHOU; Ying HAN; Qing YANG; Yuxia GAO

doi:10.16016/j.1000-5404.202011212

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Characteristics of plasma lipid metabolism and potential biomarkers in patients with acute myocardial infarction

更新时间：2026-01-09

- Characteristics of plasma lipid metabolism and potential biomarkers in patients with acute myocardial infarction
- Journal of Third Military Medical University Vol. 43, Issue 10, Pages: 970-981(2021)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202011212
  CLC：
- Received：22 November 2020，
  
  Published：30 May 2021
- 稿件说明：
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Wenxin RU, Han HU, Ting ZHOU, et al. Characteristics of plasma lipid metabolism and potential biomarkers in patients with acute myocardial infarction[J]. Journal of Third Military Medical University, 2021, 43(10): 970-981.
DOI：

Wenxin RU, Han HU, Ting ZHOU, et al. Characteristics of plasma lipid metabolism and potential biomarkers in patients with acute myocardial infarction[J]. Journal of Third Military Medical University, 2021, 43(10): 970-981. DOI： 10.16016/j.1000-5404.202011212.

摘要

Abstract

Objective

To compare the differences in plasma lipid metabolites between the patients with acute myocardial infarction (AMI) and those with normal coronary artery in order to explore the pathophysiologic mechanism and search for possible new biomarkers of AMI.

Methods

The patients undergoing coronary angiography in our hospital from September 20

2019 to January 20

2020 were enrolled in this study. According to the results

they were divided into myocardial infarction group (AMI group

=32) and control group (age- and sex-matched with the AMI group

=32). Non-targeted lipidomics analysis was performed on the blood samples to find the differences of lipid metabolites betw

een the 2 groups. Univariate and multivariate statistical analyses were applied to explore the meaningful differential metabolites

and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of the selected differential metabolites. Finally

how to disturb metabolic pathways was investigated in the AMI patients.

Results

① The orthogonal projection to latent structure discriminant analysis (OPLS-DA) and cluster heat map showed that there was a significant trend of separation between AMI group and the control group. Multivariate statistical analysis identified totally 28 differential plasma lipid metabolites

including 16 of them significantly increased and 12 decreased in the AMI group. ②There were 10 lipid metabolites such as diglyceride (DG) and phosphatidyl serine (PS) associated with an increased risk of AMI

while 13 negative predictors

including phosphatidylinositol (PI)

phosphatidylcholine (PC)

phosphatidylserine (PS)

lytic phosphatidylcholine (LPC) and triglyceride (TG)

were associated with a reduced risk of AMI. ③ROC curve identified 2 possible biomarkers of AMI

namely

PS (27∶0) (AUC=0.976) and DG(16∶0/18∶1) (AUC=0.807); ④The disturbed metabolic pathways included metabolism of glycerol phospholipid

sphingomyelin

purine and pyrimidine in the AMI patients

among which the disorder of glycerophospholipid metabolism was the most signficant.

Conclusion

The characteristics of lipid metabolism are significantly changed in AMI patients; a total of 28 differential lipid metabolites are identified

among which the disorder of glycerol phospholipid metabolism pathway indicates the most significant. PS and DG may act as the potential biomarkers for the diagnosis of AMI.

关键词

Keywords

references

GBD 2017 Causes of Death Collaborators Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017 Lancet 2018 392 10159 1736 1788 10.1016/S0140-6736(18)32203-7 GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2018, 392(10159): 1736-1788. DOI: 10.1016/S0140-6736(18)32203-7.

BENJAMIN E J VIRANI S S CALLAWAY C W Heart disease and stroke statistics-2018 update: a report from the American Heart Association Circulation 2018 137 12 e67 e492 10.1161/CIR.000000000000053 BENJAMIN E J, VIRANI S S, CALLAWAY C W, et al . Heart disease and stroke statistics-2018 update: a report from the American Heart Association[J ] . Circulation, 2018, 137(12): e67-e492. DOI: 10.1161/CIR.000000000000053.

FORD E S AJANI U A CROFT J B Explaining the decrease in U.S. deaths from coronary disease, 1980-2000 N Engl J Med 2007 356 23 2388 2398 10.1056/NEJMsa053935 FORD E S, AJANI U A, CROFT J B, et al . Explaining the decrease in U.S. deaths from coronary disease, 1980-2000[J ] . N Engl J Med, 2007, 356(23): 2388-2398. DOI: 10.1056/NEJMsa053935.

中国心血管健康与疾病报告编写组中国心血管健康与疾病报告2019概要中国循环杂志 2020 35 9 833 854 10.3969/j.issn.1000-3614.2020.09.001.Writing 中国心血管健康与疾病报告编写组. 中国心血管健康与疾病报告2019概要[J]. 中国循环杂志, 2020, 35(9): 833-854. DOI: 10.3969/j.issn.1000-3614.2020.09.001.Writing

Group for Cardiovascular Health and Diseases in China Report on cardiovascular health and diseases in China 2019: an updated summary Chin Circ J 2020 35 9 833 854 10.3969/j.issn.1000-3614.2020.09.001 Group for Cardiovascular Health and Diseases in China. Report on cardiovascular health and diseases in China 2019: an updated summary[J]. Chin Circ J, 2020, 35(9): 833-854. DOI: 10.3969/j.issn.1000-3614.2020.09.001.

USSHER J R ELMARIAH S GERSZTEN R E The emerging role of metabolomics in the diagnosis and prognosis of cardiovascular disease J Am Coll Cardiol 2016 68 25 2850 2870 10.1016/j.jacc.2016.09.972 USSHER J R, ELMARIAH S, GERSZTEN R E, et al . The emerging role of metabolomics in the diagnosis and prognosis of cardiovascular disease[J ] . J Am Coll Cardiol, 2016, 68(25): 2850-2870. DOI: 10.1016/j.jacc.2016.09.972.

WANG X WANG D WU J Metabolic characterization of myocardial infarction using GC-MS-based tissue metabolomics Int Heart J 2017 58 3 441 446 10.1536/ihj.16-432 WANG X, WANG D, WU J, et al . Metabolic characterization of myocardial infarction using GC-MS-based tissue metabolomics[J ] . Int Heart J, 2017, 58(3): 441-446. DOI: 10.1536/ihj.16-432.

吴炜王怡宁代静文原发性心肌病诊断新路径: 从高分辨影像到分子精准医学协和医学杂志 2019 10 1 12 16 10.3969/j.issn.1674-9081.2019.01.002 吴炜, 王怡宁, 代静文, 等. 原发性心肌病诊断新路径: 从高分辨影像到分子精准医学[J]. 协和医学杂志, 2019, 10(1): 12-16. DOI: 10.3969/j.issn.1674-9081.2019.01.002.

WU W WANG Y N DAI J W New clinical diagnostic pathway of primary cardiomyopathy: from high-resolution imaging to molecular precision medicine Med J PUMCH 2019 10 1 6 10 10.3969/j.issn.1674-9081.2019.01.002 WU W, WANG Y N, DAI J W, et al . New clinical diagnostic pathway of primary cardiomyopathy: from high-resolution imaging to molecular precision medicine[J ] . Med J PUMCH, 2019, 10(1): 6-10. DOI: 10.3969/j.issn.1674-9081.2019.01.002.

LANFEAR D E GIBBS J J LI J Targeted metabolomic profiling of plasma and survival in heart failure patients JACC Heart Fail 2017 5 11 823 832 10.1016/j.jchf.2017.07.009 LANFEAR D E, GIBBS J J, LI J, et al . Targeted metabolomic profiling of plasma and survival in heart failure patients[J ] . JACC Heart Fail, 2017, 5(11): 823-832. DOI: 10.1016/j.jchf.2017.07.009.

ZHENG Y YU B ALEXANDER D Metabolomics and incident hypertension among blacks: the atherosclerosis risk in communities study Hypertens Dallas Tex 2013 62 2 398 403 10.1161/HYPERTENSIONAHA.113.01166 ZHENG Y, YU B, ALEXANDER D, et al . Metabolomics and incident hypertension among blacks: the atherosclerosis risk in communities study[J ] . Hypertens Dallas Tex, 2013, 62(2): 398-403. DOI: 10.1161/HYPERTENSIONAHA.113.01166.

LAAKSONEN R EKROOS K SYSI-AHO M Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol Eur Heart J 2016 37 25 1967 1976 10.1093/eurheartj/ehw148 LAAKSONEN R, EKROOS K, SYSI-AHO M, et al . Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol[J ] . Eur Heart J, 2016, 37(25): 1967-1976. DOI: 10.1093/eurheartj/ehw148.

RELTON C L GAUNT T MCARDLE W Data resource profile: accessible resource for integrated epigenomic studies (ARIES) Int J Epidemiol 2015 44 4 1181 1190 10.1093/ije/dyv072 RELTON C L, GAUNT T, MCARDLE W, et al . Data resource profile: accessible resource for integrated epigenomic studies (ARIES)[J ] . Int J Epidemiol, 2015, 44 (4): 1181-1190. DOI: 10.1093/ije/dyv072.

IMAMURA F LEMAITRE R N KING I B Long-chain monounsaturated fatty acids and incidence of congestive heart failure in 2 prospective cohorts Circulation 2013 127 14 1512 18 1512-1521,1521e1-18 10.1161/CIRCULATIONAHA.112.001197 IMAMURA F, LEMAITRE R N, KING I B, et al . Long-chain monounsaturated fatty acids and incidence of congestive heart failure in 2 prospective cohorts[J ] . Circulation, 2013, 127(14): 1512-1521, 1521e1-18. DOI: 10.1161/CIRCULATIONAHA.112.001197.

DEL GOBBO L C IMAMURA F ASLIBEKYAN S Omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: pooling project of 19 cohort studies JAMA Intern Med 2016 176 8 1155 1166 10.1001/jamainternmed.2016.2925 DEL GOBBO L C, IMAMURA F, ASLIBEKYAN S, et al . Omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: pooling project of 19 cohort studies[J ] . JAMA Intern Med, 2016, 176(8): 1155-1166. DOI: 10.1001/jamainternmed.2016.2925.

MARKLUND M WU J H Y IMAMURA F Biomarkers of dietary omega-6 fatty acids and incident cardiovascular disease and mortality: an individual-level pooled analysis of 30 cohort studies Circulation 2019 139 21 2422 2436 10.1161/CIRCULATIONAHA.118.038908 MARKLUND M, WU J H Y, IMAMURA F, et al . Biomarkers of dietary omega-6 fatty acids and incident cardiovascular disease and mortality: an individual-level pooled analysis of 30 cohort studies [J ] . Circulation, 2019, 139(21): 2422-2436. DOI: 10.1161/CIRCULATIONAHA.118.038908.

AGEWALL S BELTRAME J F REYNOLDS H R ESC working group position paper on myocardial infarction with non-obstructive coronary arteries Eur Heart J 2017 38 3 143 153 10.1093/eurheartj/ehw149 AGEWALL S, BELTRAME J F, REYNOLDS H R, et al . ESC working group position paper on myocardial infarction with non-obstructive coronary arteries[J ] . Eur Heart J, 2017, 38(3): 143-153. DOI: 10.1093/eurheartj/ehw149.

QUEHENBERGER O DENNIS E A The human plasma lipidome N Engl J Med 2011 365 19 1812 1823 10.1056/NEJMra1104901 QUEHENBERGER O, DENNIS E A. The human plasma lipidome[J]. N Engl J Med, 2011, 365(19): 1812-1823. DOI: 10.1056/NEJMra1104901.

KOLCZYNSKA K LOZA-VALDES A HAWRO I Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review Lipids Health Dis 2020 19 1 113 10.1186/s12944-020-01286-8 KOLCZYNSKA K, LOZA-VALDES A, HAWRO I, et al . Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review[J ] . Lipids Health Dis, 2020, 19(1): 113. DOI: 10.1186/s12944-020-01286-8.

EGAN B M Plasma lipidomic profile signature of hypertension in Mexican American families: specific role of diacylglycerols Hypertension 2013 62 3 621 626 10.1161/HYPERTENSIONAHA.113.01633 EGAN B M. Plasma lipidomic profile signature of hypertension in Mexican American families: specific role of diacylglycerols[J]. Hypertension, 2013, 62(3): 621-626. DOI: 10.1161/HYPERTENSIONAHA.113.01633.

KRIS-ETHERTON P M YU S Individual fatty acid effects on plasma lipids and lipoproteins: human studies Am J Clin Nutr 1997 65 1628S 1644S 10.1016/S0271-5317(97)00070-5 KRIS-ETHERTON P M, YU S. Individual fatty acid effects on plasma lipids and lipoproteins: human studies[J]. Am J Clin Nutr, 1997, 65: 1628S-1644S. DOI: 10.1016/S0271- 5317(97)00070-5.

LU J CHEN B CHEN T Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases Redox Biol 2017 12 899 907 10.1016/j.redox.2017.04.032 LU J, CHEN B, CHEN T, et al . Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases[J ] . Redox Biol, 2017, 12: 899-907. DOI: 10.1016/j.redox.2017.04.032.

FLOEGEL A KVHN T SOOKTHAI D Serum metabolites and risk of myocardial infarction and ischemic stroke: a targeted metabolomic approach in two German prospective cohorts Eur J Epidemiol 2018 33 1 55 66 10.1007/s10654-017-0333-0 FLOEGEL A, KVHN T, SOOKTHAI D, et al . Serum metabolites and risk of myocardial infarction and ischemic stroke: a targeted metabolomic approach in two German prospective cohorts[J ] . Eur J Epidemiol, 2018, 33(1): 55-66. DOI: 10.1007/s10654-017-0333-0.

SARRI E GARCIA-DORADO D ABELLAN A Effects of hypoxia, glucose deprivation and acidosis on phosphatidylcholine synthesis in HL-1 cardiomyocytes. CTP: phosphocholine cytidylyltransferase activity correlates with sarcolemmal disruption Biochem J 2006 394 Pt 1 325 334 10.1042/BJ20050834 SARRI E, GARCIA-DORADO D, ABELLAN A, et al . Effects of hypoxia, glucose deprivation and acidosis on phosphatidylcholine synthesis in HL-1 cardiomyocytes. CTP: phosphocholine cytidylyltransferase activity correlates with sarcolemmal disruption[J ] . Biochem J, 2006, 394(Pt 1): 325-334. DOI: 10.1042/BJ20050834.

BRÜHL A HAFNER G LöFFELHOLZ K Release of choline in the isolated heart, an indicator of ischemic phospholipid degradation and its protection by ischemic preconditioning: no evidence for a role of phospholipase D Life Sci 2004 75 13 1609 1620 10.1016/j.lfs.2004.03.019 BRÜHL A, HAFNER G, LöFFELHOLZ K. Release of choline in the isolated heart, an indicator of ischemic phospholipid degradation and its protection by ischemic preconditioning: no evidence for a role of phospholipase D[J]. Life Sci, 2004, 75(13): 1609-1620. DOI: 10.1016/j.lfs.2004.03.019.

SUTTER I KlINGENBERG R OTHMAN A Decreased phosphatidylcholine plasmalogens—A putative novel lipid signature in patients with stable coronary artery disease and acute myocardial infarction Atherosclerosis 2016 246 130 140 10.1016/j.atherosclerosis.2016.01.003 SUTTER I, KlINGENBERG R, OTHMAN A, et al . Decreased phosphatidylcholine plasmalogens—A putative novel lipid signature in patients with stable coronary artery disease and acute myocardial infarction[J ] . Atherosclerosis, 2016, 246: 130-140. DOI: 10.1016/j.atherosclerosis.2016.01.003.

LAW S H CHAN M L MARATHE G K An updated review of lysophosphatidylcholine metabolism in human diseases Int J Mol Sci 2019 20 5 10.3390/ijms20051149 LAW S H, CHAN M L, MARATHE G K, et al . An updated review of lysophosphatidylcholine metabolism in human diseases[J ] . Int J Mol Sci, 2019, 20(5). DOI: 10.3390/ijms20051149.

ZHU M HAN Y ZHANG Y Metabolomics study of the biochemical changes in the plasma of myocardial infarction patients Front Physiol 2018 9 1017 10.3389/fphys.2018.01017 ZHU M, HAN Y, ZHANG Y, et al . Metabolomics study of the biochemical changes in the plasma of myocardial infarction patients[J ] . Front Physiol, 2018, 9: 1017. DOI: 10.3389/fphys.2018.01017.

WHITE A J DUFFY S J WALTON A S Matrix metalloproteinase-3 and coronary remodelling: implications for unstable coronary disease Cardiovasc Res 2007 75 4 813 820 10.1016/j.cardiores.2007.05.003 WHITE A J, DUFFY S J, WALTON A S, et al . Matrix metalloproteinase-3 and coronary remodelling: implications for unstable coronary disease[J ] . Cardiovasc Res, 2007, 75(4): 813-820. DOI: 10.1016/j.cardiores.2007.05.003.

MEIKLE P J WONG G TSOROTES D Plasma lipidomic analysis of stable and unstable coronary artery disease Arterioscler Thromb Vasc Biol 2011 31 11 2723 2732 10.1161/atvbaha.111.234096 MEIKLE P J, WONG G, TSOROTES D, et al . Plasma lipidomic analysis of stable and unstable coronary artery disease[J ] . Arterioscler Thromb Vasc Biol, 2011, 31(11): 2723- 2732. DOI: 10.1161/atvbaha.111.234096.

YANG Q GUO M ZHOU Y Phosphatidylserine-specific phospholipase A1 is the critical bridge for hepatitis C virus assembly Virol Sin 2019 34 5 521 537 10.1007/s12250-019-00123-2 YANG Q, GUO M, ZHOU Y, et al . Phosphatidylserine-specific phospholipase A1 is the critical bridge for hepatitis C virus assembly[J ] . Virol Sin, 2019, 34(5): 521-537. DOI: 10.1007/s12250-019-00123-2.

KURANO M DOHI T NOJIRI T Blood levels of serotonin are specifically correlated with plasma lysophosphatidylserine among the glycero-lysophospholipids BBA Clin 2015 4 92 98 10.1016/j.bbacli.2015.08.003 KURANO M, DOHI T, NOJIRI T, et al . Blood levels of serotonin are specifically correlated with plasma lysophosphatidylserine among the glycero-lysophospholipids[J ] . BBA Clin, 2015, 4: 92-98. DOI: 10.1016/j.bbacli.2015.08.003.

YANO M WATANABE K YAMAMOTO T Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null mice J Biol Chem 2011 286 5 3992 4002 10.1074/jbc.M110.179176 YANO M, WATANABE K, YAMAMOTO T, et al . Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null mice[J ] . J Biol Chem, 2011, 286(5): 3992-4002. DOI: 10.1074/jbc.M110.179176.

JIANG X C PAULTRE F PEARSON T A Plasma sphingomyelin level as a risk factor for coronary artery disease Arterioscler Thromb Vasc Biol 2000 20 2614 2618 10.1161/01.atv.20.12.2614 JIANG X C, PAULTRE F, PEARSON T A, et al . Plasma sphingomyelin level as a risk factor for coronary artery disease[J ] . Arterioscler Thromb Vasc Biol, 2000, 20: 2614-2618. DOI: 10.1161/01.atv.20.12.2614.

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