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Koroner anjiyografi hastalarında serbest amino asit profili değişiklikleri: koroner arter hastalığı için potansiyel biyobelirteçler

Year 2025, Volume: 50 Issue: 3, 645 - 653, 30.09.2025
https://doi.org/10.17826/cumj.1663964

Abstract

Amaç: Bu çalışma, koroner anjiyografi (KA) uygulanan hastalarda plazma amino asit profilini belirlemeyi ve Koroner arter hastalığı (KAH) ile ilişkili potansiyel biyobelirteçleri tanımlamayı amaçlamaktadır.
Gereç ve Yöntem: Hedeflenen metabolomik yaklaşım kullanılarak, 25 KAH hastasının (KA öncesi ve sonrası) ve 25 sağlıklı kontrolün plazmasındaki 41 amino asit düzeyi analiz edildi. KA öncesi ve sonrası hastalardan ve sağlıklı kontrollerden alınan plazma örnekleri, serbest amino asit profillerini belirlemek için yüksek performanslı sıvı kromatografisi tandem kütle spektrometrisi (LC-MS/MS) kullanılarak analiz edildi. Amino asit konsantrasyonları ölçüldü.
Bulgular: KA öncesi hastalarda, arjinin (35.124±14.476 µmol/L), asparajin (34.386±6.41 µmol/L), aspartik asit (11.266±4.788 µmol/L), glutamik asit (136.502±54.193 µmol/L) ve dallı zincirli amino asitlerden lösin (168.451±85.247 µmol/L) ile izolösin (66.067±14.605 µmol/L) düzeyleri kontrol grubuna kıyasla belirgin şekilde daha düşüktü. Buna karşılık, hidroksiprolin (27.16±21.173 µmol/L), hidroksilizin (0.21±0.116 µmol/L), sistin (27.039±11.978 µmol/L) ve etanolamin (13.136±5.812 µmol/L) düzeyleri artmıştı. KA sonrası dönemde ise asparajin (30.408±7.121 µmol/L), lösin (106.362 ± 25.446 µmol/L), izolösin (57.637±11.83 µmol/L), treonin (81.422±16.043 µmol/L) ve triptofan (36.548±12.014 µmol/L) düzeylerinde ek azalmalar gözlendi.
Sonuç: Bu bulgular, amino asit profillemesinin KAH için tanısal ve terapötik bir araç olarak potansiyelini vurgulamakta olup, hastalık patogenezine ilişkin içgörüler ve hedefli müdahaleler için fırsatlar sunmaktadır.

Project Number

20103

References

  • Mirzaei H, Suarez JA, Longo VD. Protein and amino acid restriction, aging and disease: from yeast to humans. Trends Endocrinol Metab. 2014;25:558-66.
  • Hollywood K, Brıson DR, Goodacre R. Metabolomics: current technologies and future trends. Proteomics. 2006;6:4716-23.
  • Cheng ML, Wang CH, Shiao MS, Liu MH, Huang YY, Huang CY et al. Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics. J Am Coll Cardiol. 2015;65:1509-20.
  • Huang Q, Tan Y, Yin P, Ye G, Gao P, Lu X et al. Metabolic characterization of hepatocellular carcinoma using nontargeted tissue metabolomics. Cancer Res. 2013;73:4992-5002.
  • Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009;457:910-14.
  • Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet. 2010;3:207-14.
  • Xuan C, Li H, Tian QW, Guo JJ, He GW, Lun LM et al. Quantitative assessment of serum amino acids and association with early-onset coronary artery disease. Clin Interv Aging. 2021;16:465.
  • Mu H, Wang X, Yang R, Wang S, Zhang W, Li H et al. The association of aromatic amino acids with coronary artery disease and major adverse cardiovascular events in a Chinese population. Int J Food Sci Nutr. 2024;75:825-34.
  • Prechtl L, Carrard J, Gallart-Ayala H, Borreggine R, Teav T, Königstein K et al. Circulating amino acid signature features urea cycle alterations associated with coronary artery disease. Sci Rep. 2024;14:25848.
  • Zhao Y, Li Y, Wang F, Lv H, Qu Y, Qi L et al. Improved risk prediction of acute myocardial infarction in patients with stable coronary artery disease using an amino acid-assisted model. Cardiovasc Ther. 2024;9935805.
  • Yu Q, Zhao F, Wang S, Jia X, Shen S, Zhao X et al. The diagnostic value of bile acids and amino acids in differentiating acute coronary syndromes. Int J Gen Med. 2025;18:179-89.
  • Vickers NJ. Animal communication: when i’m calling you, will you answer too?. Curr Biol. 2017;27:713-15.
  • Qi L, Qi Q, Prudente S, Mendonca C, Andreozzi F, di Pietro N et al. Association between a genetic variant related to glutamic acid metabolism and coronary heart disease in individuals with type 2 diabetes. JAMA. 2013;310:821-28.
  • Thackeray JT, Bankstahl JP, Wang Y, Wollert KC, Bengel FM. Targeting amino acid metabolism for molecular imaging of inflammation early after myocardial infarction. Theranostics. 2016;6:1768-79.
  • Zhu Q, Wu Y, Mai J, Guo G, Meng J, Fang X et al. Comprehensive metabolic profiling of inflammation indicated key roles of glycerophospholipid and arginine metabolism in coronary artery disease. Front Immunol. 2022;13:829425.
  • Patel RS, Ghasemzadeh N, Eapen DJ, Sher S, Arshad S, Ko YA et al. Novel biomarker of oxidative stress is associated with risk of death in patients with coronary artery disease. Circulation. 2016;133:361-69.
  • Karna E, Szoka L, Huynh TYL, Palka JA. Proline-dependent regulation of collagen metabolism. Cell Mol Life Sci. 2019;77:1911-18.
  • Patriarca EJ, Cermola F, d'Aniello C, Fico A, Guardiola O, De Cesare D et al. The multifaceted roles of proline in cell behavior. Front Cell Dev Biol. 2021;9:728576.
  • Obeid OA. Plasma amino acid concentrations in patients with coronary heart disease: a comparison between UK Indian Asian and Caucasian men. Int J Vitam Nutr Res. 2005;75:267-73.
  • Lima A, Ferin R, Fontes A, Santos E, Martins D, Baptista J et al. Cysteine is a better predictor of coronary artery disease than conventional homocysteine in high-risk subjects under preventive medication. Nutr Metab Cardiovasc Dis. 2020;30:1281-88.
  • Rom O, Aviram M. It is not just lipids: proatherogenic vs. antiatherogenic roles for amino acids in macrophage foam cell formation. Curr Opin Lipidol. 2017;28:85-7.
  • Tobias DK, Lawler PR, Harada PH, Demler OV, Ridker PM, Manson JE, Cheng S, Mora S. Circulating branched-chain amino acids and incident cardiovascular disease in a prospective cohort of US women. Circ Genom Precis Med. 2018;11:e002157.
  • Zaric BL, Radovanovic JN, Gluvic Z, Stewart AJ, Essack M, Motwalli O et al. Atherosclerosis linked to aberrant amino acid metabolism and immunosuppressive amino acid catabolizing enzymes. Front Immunol. 2020;11:551758.
  • Zhang SY, Xuan C, Zhang XC, Zhu J, Yue K, Zhao P et al. Association between MTHFR gene common variants, serum homocysteine, and risk of early-onset coronary artery disease: a case–control study. Biochem Genet. 2020;58:245-56.
  • Fan Y, Li Y, Chen Y, Zhao YJ, Liu LW, Li J et al. Comprehensive metabolomic characterization of coronary artery diseases. J Am Coll Cardiol. 2016;68:1281-93.
  • Sharma K. Myeloperoxidase activity and oxidized amino acids as biomarkers in chronic kidney disease and coronary artery disease. Am J Nephrol. 2017;46:71-3.
  • Zhang S, Zhang S, Wang H, Wu W, Ye Y. Arginine methylation dysfunction increased risk of acute coronary syndrome in coronary artery disease population: a case-control study. Medicine. 2017;96:e6074.
  • Wang L, Liu S, Yang W, Yu H, Zhang L, Ma P et al. Plasma amino acid profile in patients with aortic dissection. Sci Rep. 2017;10:40146.
  • Ottosson F, Smith E, Melander O, Fernandez C. Altered asparagine and glutamate homeostasis precede coronary artery disease and type 2 diabetes. J Clin Endocrinol Metab. 2018;103:3060-69.
  • Grajeda-Iglesias C, Aviram M. Specific amino acids affect cardiovascular diseases and atherogenesis via protection against macrophage foam cell formation. Rambam Maimonides Med J. 2018;9:e0022.
  • Qaradakhi T, Gadanec LK, McSweeney KR, Abraham JR, Apostolopoulos V, Zulli A. The anti-inflammatory effect of taurine on cardiovascular disease. Nutrients. 2020;12:2847

Free amino acid profile changes in coronary angiography patients: potential biomarkers for coronary artery disease

Year 2025, Volume: 50 Issue: 3, 645 - 653, 30.09.2025
https://doi.org/10.17826/cumj.1663964

Abstract

Purpose: This study aims to delineate the plasma amino acid profile in patients undergoing coronary angiography (CA) and identify potential biomarkers associated with Coronary artery disease (CAD).
Materials and Methods: A targeted metabolomics approach was employed to analyze plasma levels of 41 amino acids in 25 CAD patients (pre- and post-CA) and 25 healthy controls. Plasma samples from patients pre- and post-CA, as well as from healthy controls, were analyzed using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine free amino acid profiles. Amino acid concentrations were quantified.
Results: In pre-CA patients, levels of arginine (35.124±14.476 µmol/L), asparagine (34.386±6.41 µmol/L), aspartic acid (11.266±4.788 µmol/L), glutamic acid (136.502±54.193µmol/L), and branched-chain amino acids such as leucine (168.451±85.247µmol/L) and isoleucine (66.067±14.605 µmol/L) were markedly lower than in controls. Conversely, hydroxyproline (27.16±21.173 µmol/L), hydroxylysine (0.21±0.116µmol/L), cystine (27.039±11.978 µmol/L), and ethanolamine (13.136±5.812 µmol/L) were elevated. Post-CA, further reductions were observed in asparagine (30.408±7.121µmol/L), leucine (106.362±25.446 µmol/L), isoleucine (57.637±11.83 µmol/L), threonine (81.422±16.043 µmol/L), and tryptophan (36.548±12.014 µmol/L).
Conclusion: These findings highlight the potential of amino acid profiling as a diagnostic and therapeutic tool for CAD, providing insights into disease pathogenesis and opportunities for targeted interventions.

Supporting Institution

This study received support from Harran University Scientific Research Projects Unit, project number 20103.

Project Number

20103

Thanks

Thanks Harran University Scientific Research Projects Unit

References

  • Mirzaei H, Suarez JA, Longo VD. Protein and amino acid restriction, aging and disease: from yeast to humans. Trends Endocrinol Metab. 2014;25:558-66.
  • Hollywood K, Brıson DR, Goodacre R. Metabolomics: current technologies and future trends. Proteomics. 2006;6:4716-23.
  • Cheng ML, Wang CH, Shiao MS, Liu MH, Huang YY, Huang CY et al. Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics. J Am Coll Cardiol. 2015;65:1509-20.
  • Huang Q, Tan Y, Yin P, Ye G, Gao P, Lu X et al. Metabolic characterization of hepatocellular carcinoma using nontargeted tissue metabolomics. Cancer Res. 2013;73:4992-5002.
  • Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009;457:910-14.
  • Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet. 2010;3:207-14.
  • Xuan C, Li H, Tian QW, Guo JJ, He GW, Lun LM et al. Quantitative assessment of serum amino acids and association with early-onset coronary artery disease. Clin Interv Aging. 2021;16:465.
  • Mu H, Wang X, Yang R, Wang S, Zhang W, Li H et al. The association of aromatic amino acids with coronary artery disease and major adverse cardiovascular events in a Chinese population. Int J Food Sci Nutr. 2024;75:825-34.
  • Prechtl L, Carrard J, Gallart-Ayala H, Borreggine R, Teav T, Königstein K et al. Circulating amino acid signature features urea cycle alterations associated with coronary artery disease. Sci Rep. 2024;14:25848.
  • Zhao Y, Li Y, Wang F, Lv H, Qu Y, Qi L et al. Improved risk prediction of acute myocardial infarction in patients with stable coronary artery disease using an amino acid-assisted model. Cardiovasc Ther. 2024;9935805.
  • Yu Q, Zhao F, Wang S, Jia X, Shen S, Zhao X et al. The diagnostic value of bile acids and amino acids in differentiating acute coronary syndromes. Int J Gen Med. 2025;18:179-89.
  • Vickers NJ. Animal communication: when i’m calling you, will you answer too?. Curr Biol. 2017;27:713-15.
  • Qi L, Qi Q, Prudente S, Mendonca C, Andreozzi F, di Pietro N et al. Association between a genetic variant related to glutamic acid metabolism and coronary heart disease in individuals with type 2 diabetes. JAMA. 2013;310:821-28.
  • Thackeray JT, Bankstahl JP, Wang Y, Wollert KC, Bengel FM. Targeting amino acid metabolism for molecular imaging of inflammation early after myocardial infarction. Theranostics. 2016;6:1768-79.
  • Zhu Q, Wu Y, Mai J, Guo G, Meng J, Fang X et al. Comprehensive metabolic profiling of inflammation indicated key roles of glycerophospholipid and arginine metabolism in coronary artery disease. Front Immunol. 2022;13:829425.
  • Patel RS, Ghasemzadeh N, Eapen DJ, Sher S, Arshad S, Ko YA et al. Novel biomarker of oxidative stress is associated with risk of death in patients with coronary artery disease. Circulation. 2016;133:361-69.
  • Karna E, Szoka L, Huynh TYL, Palka JA. Proline-dependent regulation of collagen metabolism. Cell Mol Life Sci. 2019;77:1911-18.
  • Patriarca EJ, Cermola F, d'Aniello C, Fico A, Guardiola O, De Cesare D et al. The multifaceted roles of proline in cell behavior. Front Cell Dev Biol. 2021;9:728576.
  • Obeid OA. Plasma amino acid concentrations in patients with coronary heart disease: a comparison between UK Indian Asian and Caucasian men. Int J Vitam Nutr Res. 2005;75:267-73.
  • Lima A, Ferin R, Fontes A, Santos E, Martins D, Baptista J et al. Cysteine is a better predictor of coronary artery disease than conventional homocysteine in high-risk subjects under preventive medication. Nutr Metab Cardiovasc Dis. 2020;30:1281-88.
  • Rom O, Aviram M. It is not just lipids: proatherogenic vs. antiatherogenic roles for amino acids in macrophage foam cell formation. Curr Opin Lipidol. 2017;28:85-7.
  • Tobias DK, Lawler PR, Harada PH, Demler OV, Ridker PM, Manson JE, Cheng S, Mora S. Circulating branched-chain amino acids and incident cardiovascular disease in a prospective cohort of US women. Circ Genom Precis Med. 2018;11:e002157.
  • Zaric BL, Radovanovic JN, Gluvic Z, Stewart AJ, Essack M, Motwalli O et al. Atherosclerosis linked to aberrant amino acid metabolism and immunosuppressive amino acid catabolizing enzymes. Front Immunol. 2020;11:551758.
  • Zhang SY, Xuan C, Zhang XC, Zhu J, Yue K, Zhao P et al. Association between MTHFR gene common variants, serum homocysteine, and risk of early-onset coronary artery disease: a case–control study. Biochem Genet. 2020;58:245-56.
  • Fan Y, Li Y, Chen Y, Zhao YJ, Liu LW, Li J et al. Comprehensive metabolomic characterization of coronary artery diseases. J Am Coll Cardiol. 2016;68:1281-93.
  • Sharma K. Myeloperoxidase activity and oxidized amino acids as biomarkers in chronic kidney disease and coronary artery disease. Am J Nephrol. 2017;46:71-3.
  • Zhang S, Zhang S, Wang H, Wu W, Ye Y. Arginine methylation dysfunction increased risk of acute coronary syndrome in coronary artery disease population: a case-control study. Medicine. 2017;96:e6074.
  • Wang L, Liu S, Yang W, Yu H, Zhang L, Ma P et al. Plasma amino acid profile in patients with aortic dissection. Sci Rep. 2017;10:40146.
  • Ottosson F, Smith E, Melander O, Fernandez C. Altered asparagine and glutamate homeostasis precede coronary artery disease and type 2 diabetes. J Clin Endocrinol Metab. 2018;103:3060-69.
  • Grajeda-Iglesias C, Aviram M. Specific amino acids affect cardiovascular diseases and atherogenesis via protection against macrophage foam cell formation. Rambam Maimonides Med J. 2018;9:e0022.
  • Qaradakhi T, Gadanec LK, McSweeney KR, Abraham JR, Apostolopoulos V, Zulli A. The anti-inflammatory effect of taurine on cardiovascular disease. Nutrients. 2020;12:2847
There are 31 citations in total.

Details

Primary Language English
Subjects Clinical Sciences (Other), Metabolic Medicine, Medical Biochemistry - Amino Acids and Metabolites
Journal Section Research
Authors

Reşat Dikme 0000-0001-9157-7830

İsmail Yarcan This is me 0000-0002-8566-3983

Project Number 20103
Publication Date September 30, 2025
Submission Date March 23, 2025
Acceptance Date July 31, 2025
Published in Issue Year 2025 Volume: 50 Issue: 3

Cite

MLA Dikme, Reşat and İsmail Yarcan. “Free Amino Acid Profile Changes in Coronary Angiography Patients: Potential Biomarkers for Coronary Artery Disease”. Cukurova Medical Journal, vol. 50, no. 3, 2025, pp. 645-53, doi:10.17826/cumj.1663964.