Bioinformatics Analysis to Find Novel Biomarkers for Coronary Heart Disease
-
Akram Gholipour
,
Farshad Shakerian
,
Ali Zahedmehr
,
Shiva Irani
,
Mahshid Malakootian
,
Seyed Javad Mowla
Abstract
Background: Coronary heart disease (CHD), a major cause of death worldwide, is defined as a narrowing or blockage of the coronary arteries that supply oxygen and blood to the heart. We aimed to find potential biomarkers for coronary artery disease, by comparing the expression profile of blood exosomes of both normal and CHD samples.
Methods: Datasets of 6 CHD and 6 normal samples of blood exosomes were downloaded, and differentially expressed RNAs, with adjusted P<0.01 and log2FoldChange≥1 were achieved. Moreover, gene ontology (GO) and pathway analysis were accomplished by PANTHER database for datasets.
Results: Our data analysis found 119 differentially expressed genes between two datasets. By comparing transcriptome profiles, we candidate the highest downregulated gene, ACSBG1, and the highest upregulated one, DEFA4, as specific biomarkers for CHD. Furthermore, GO and pathway analysis depicted that aforementioned differentially expressed genes are mostly involved in different molecular metabolic process, inflammation, immune system process and response to stimulus pathways which all cause cardiovascular diseases.
Conclusion: We have provided new potential biomarkers for CHD, though experimental validation is still needed to confirm the suitability of the candidate genes for early detection of CHD.
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29. Winter J, Pantelis A, Kraus D, et al (2011). Human α-Defensin (DEFA) Gene Expression Helps to Characterise Benign and Malignant Salivary Gland Tumours. BMC Cancer, 12: 465.
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31. Libby P (2006). Inflammation and Cardio-vascular Disease Mechanisms. Am J Clin Nutr, 83 (2): 456S-460S.
32. Li JJ (2011). Inflammation in Coronary Ar-tery Diseases. Chin Med J (Engl), 124 (21): 3568-3575.
33. Steven S, Frenis K, Oelze M, et al (2019). Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease. Oxid Med Cell Longev, 2019:7092151.
34. Zhang Y, Liu Y, Liu H, et al (2019). Exo-somes: Biogenesis, Biologic Function and Clinical Potential. Cell & Bioscience, 9: 19.
35. Colombo M, Raposo G, Thery C (2014). Biogenesis, Secretion, and Intercellular In-teractions of Exosomes and Other Ex-tracellular Vesicles. Annu Rev Cell Dev Biol, 30: 255-89.
36. Nozaki T, Sugiyama S, Koga H, et al (2009). Significance of a Multiple Biomarkers Strategy Including Endothelial Dysfunc-tion to Improve Risk Stratification for Cardiovascular Events in Patients at High Risk for Coronary Heart Disease. J Am Coll Cardiol, 54 (7): 601-8.
37. Amabile N, Cheng S, Renard J M, et al (2014). Association of Circulating Endo-thelial Microparticles With Cardiometa-bolic Risk Factors in the Framingham Heart Study. Eur Heart J, 35 (42): 2972-9.
38. Zhang Y, Vernooij F, Ibrahim I, et al (2016). Extracellular Vesicle Proteins Associated With Systemic Vascular Events Correlate With Heart Failure: An Observational Study in a Dyspnoea Cohort. PLoS One, 11 (1): e0148073.
2. Sanchis-Gomar F, Perez-Quilis C, Leischik R, et al (2016). Epidemiology of coronary heart disease and acute coronary syn-drome. Ann Transl Med, 4 (13): 256.
3. Charlson FJ, Moran AE, Freedman G, et al (2013). The contribution of major de-pression to the global burden of ischemic heart disease: a comparative risk assess-ment. BMC Med, 11: 250.
4. Ambrose John A, Singh M (2015). Patho-physiology of coronary artery disease leading to acute coronary syndromes. F1000Prime Rep, 7: 08.
5. Parsanathan R, K.Jain S (2020). Novel Inva-sive and Noninvasive Cardiac-Specific Biomarkers in Obesity and Cardiovascu-lar Diseases. Metab syndr Relat Disord, 18 (1): 10-30.
6. Mirzadeh Azad F, Arabian M, Maleki M, et al (2020). Small Molecules with Big Im-pacts on Cardiovascular Diseases. Biochem Genet, 58 (3): 359–383.
7. Malakootian M, Mirzadeh Azad F, Naeli P, et al (2017). Novel Spliced Variants of OCT4, OCT4C and OCT4C1, With Dis-tinct Expression Patterns and Functions in Pluripotent and Tumor Cell Lines. Eur J Cell Biol, 96 (4): 347-355.
8. Md Arshad MK, Mohamad Fathil MF, C B Gopinath S, et al (2016). Cardiac Bi-omarkers: Invasive to Non-invasive As-sessments. Curr Med Chem, 23 (37): 4270-4284.
9. Mayeux R (2004). Biomarkers: Potential Us-es and Limitations. NeuroRx, 1 (2): 182-188.
10. Samanta S, Rajasingh Sh, Drosos N, et al (2018). Exosomes: New Molecular Tar-gets of Diseases. Acta Pharmacol Sin, 39 (4): 501-513.
11. Rani B, VK Sharma (2017). Transcriptome profiling: methods and applications- A review. Agric Rev, 38 (4): 271-281.
12. Shengli L, Yuchen L, Bing Ch, et al (2018). exoRBase: a database of circRNA, lncRNA and mRNA in human blood exosomes. Nucleic Acids Res, 46: 106-112.
13. Dhingra R, Ramachandran SV (2017). Bi-omarkers in Cardiovascular Disease: Sta-tistical Assessment and Section on Key Novel Heart Failure Biomarkers. Trends Cardiovasc Med, 27 (2): 123-133.
14. Mark Richards A (2018). Future biomarkers in cardiology: my favourites. Eur Heart J Suppl, 20: 37-44.
15. Weinberg E, Shimpo M, W De Keulenaer G, et al (2002). Expression and Regula-tion of ST2, an interleukin-1 Receptor Family Member, in Cardiomyocytes and Myocardial Infarction. Circulation, 106 (23): 2961-2966.
16. Weinberg, E.O (2009). ST2 Protein in Heart Disease: From Discovery to Mechanisms and Prognostic Value. Biomark Med, 3 (5): 495-511.
17. Wollert, K.C (2007). Growth-differentiation factor-15 in Cardiovascular Disease: From Bench to Bedside, and Back. Basic Res Cardiol, 102 (5):412-5.
18. Antoon Siemelink M, Zeller T (2014). Bi-omarkers of Coronary Artery Disease: The Promise of the Transcriptome. Curr Cardiol Rep, 16 (8): 513.
19. Plebani, M (2001). Biochemical Markers of Cardiac Damage: From Efficiency to Ef-fectiveness. Clin Chim Acta, 311 (1): 3-7.
20. Albus Ch, Barkhausen J, Fleck E, et al (2017). The Diagnosis of Chronic Coro-nary Heart Disease. Dtsch Arztebl Int, 114 (42): 712–719.
21. Steinberg S J, Morgenthaler J, Heinzer A K, et al (2000). Very Long-Chain acyl-CoA Synthetases. Human "Bubblegum" Rep-resents a New Family of Proteins Capa-ble of Activating Very Long-Chain Fatty Acids. J Biol Chem, 275 (45): 35162-9.
22. Watkins P A, Maiguel D, Jia Zh, et al (2007). Evidence for 26 Distinct Acyl-Coenzyme A Synthetase Genes in the Human Ge-nome. J Lipid Res, 48 (12): 2736-50.
23. Gudjonsson J E, Ding J, Li X, et al (2009). Global Gene Expression Analysis Re-veals Evidence for Decreased Lipid Bio-synthesis and Increased Innate Immunity in Uninvolved Psoriatic Skin. J Invest Der-matol, 129 (12): 2795-804.
24. Kannel W B, Vasan, R.S (2009). Triglycerides as Vascular Risk Factors: New Epidemio-logic Insights. Curr Opin Cardiol, 24 (4): 345-50.
25. Smolders B, Lemmens R, Thijs V (2007). Lipoprotein (A) and Stroke: A Meta-Analysis of Observational Studies. Stroke, 38 (6): 1959-66.
26. Lu H, Chen Y, Li L (2018). Metabolic Path-way Genes Associated with Susceptibility Genes to Coronary Artery Disease. Int J Genomics, 2018:9025841.
27. Faurschou M, Borregaard N (2003). Neu-trophil Granules and Secretory Vesicles in Inflammation. Microbes Infect, 5 (14): 1317-27.
28. Agerberth B, Charo J, Werr J, et al (2000). The Human Antimicrobial and Chemo-tactic Peptides LL-37 and Alpha-Defensins Are Expressed by Specific Lymphocyte and Monocyte Populations. Blood, 96 (9): 3086-93.
29. Winter J, Pantelis A, Kraus D, et al (2011). Human α-Defensin (DEFA) Gene Expression Helps to Characterise Benign and Malignant Salivary Gland Tumours. BMC Cancer, 12: 465.
30. Entman M L, Youker K, Shoji T, et al (1992). Neutrophil Induced Oxidative In-jury of Cardiac Myocytes. A Compart-mented System Requiring CD11b/CD18-ICAM-1 Adherence. J Clin Invest, 90 (4): 1335-45.
31. Libby P (2006). Inflammation and Cardio-vascular Disease Mechanisms. Am J Clin Nutr, 83 (2): 456S-460S.
32. Li JJ (2011). Inflammation in Coronary Ar-tery Diseases. Chin Med J (Engl), 124 (21): 3568-3575.
33. Steven S, Frenis K, Oelze M, et al (2019). Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease. Oxid Med Cell Longev, 2019:7092151.
34. Zhang Y, Liu Y, Liu H, et al (2019). Exo-somes: Biogenesis, Biologic Function and Clinical Potential. Cell & Bioscience, 9: 19.
35. Colombo M, Raposo G, Thery C (2014). Biogenesis, Secretion, and Intercellular In-teractions of Exosomes and Other Ex-tracellular Vesicles. Annu Rev Cell Dev Biol, 30: 255-89.
36. Nozaki T, Sugiyama S, Koga H, et al (2009). Significance of a Multiple Biomarkers Strategy Including Endothelial Dysfunc-tion to Improve Risk Stratification for Cardiovascular Events in Patients at High Risk for Coronary Heart Disease. J Am Coll Cardiol, 54 (7): 601-8.
37. Amabile N, Cheng S, Renard J M, et al (2014). Association of Circulating Endo-thelial Microparticles With Cardiometa-bolic Risk Factors in the Framingham Heart Study. Eur Heart J, 35 (42): 2972-9.
38. Zhang Y, Vernooij F, Ibrahim I, et al (2016). Extracellular Vesicle Proteins Associated With Systemic Vascular Events Correlate With Heart Failure: An Observational Study in a Dyspnoea Cohort. PLoS One, 11 (1): e0148073.
| Files | ||
| Issue | Vol 51 No 5 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v51i5.9430 | |
| Keywords | ||
| Blood exosomes Coronary heart disease Differentially expressed genes | ||
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How to Cite
1.
Gholipour A, Shakerian F, Zahedmehr A, Irani S, Malakootian M, Mowla SJ. Bioinformatics Analysis to Find Novel Biomarkers for Coronary Heart Disease. Iran J Public Health. 2022;51(5):1152-1160.
