Research Article


DOI :10.26650/JARHS2024-1397075   IUP :10.26650/JARHS2024-1397075    Full Text (PDF)

LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS

Fuat KarakuşBurak Kuzu

Objective: Cardiovascular disease causing the most deaths worldwide is ischaemic heart disease. In addition to modifiable and non-modifiable risk factors, there is a growing consideration that environmental factors, especially heavy metals, may also contribute to the risk of ischaemic heart disease. The study identified the potential molecular mechanisms associated with ischaemic heart disease induced by arsenic, cadmium, lead, and mercury.

Materials and Methods: In this study, we used toxicogenomic data and various bioinformatic databases and tools, including the Comparative Toxicogenomic Database, ToppGene Suite, GeneMANIA, String, Cytoscape, CHEA3, and MIENTURNET.

Results: We observed an overlap of the CRP, HMOX1, PON1, and PTGS2 genes among the metals and ischaemic heart disease. The most prevalent interactions among these genes were identified as physical interactions, constituting 77.64% of the total. Several pathways were determined as the principal molecular mechanisms that might be influenced by the examined metals involved in the aetiology of ischaemic heart disease (e.g., regulation of plasma lipoprotein particle levels, response to inorganic substances, blood circulation, circulatory system processes, and cellular response to metal ions). CRP and HMOX1 emerged as key genes, whereas CREB3L3 and ATF5 were identified as key transcription factors related to ischaemic heart disease caused by the combination of the examined metals. Furthermore, we identified two miRNAs (hsa-miR-128-3p and hsa miR-1273g-3p) associated with ischaemic heart disease.

Conclusion: These observations make a substantial contribution to our understanding of the processes underlying ischaemic heart disease induced by arsenic, cadmium, lead, and mercury.

DOI :10.26650/JARHS2024-1397075   IUP :10.26650/JARHS2024-1397075    Full Text (PDF)

METAL MARUZİYETİNİN İSKEMİ KALP HASTALIĞIYLA BAĞLANTISI: BİYOİNFORMATİK ANALİZ

Fuat KarakuşBurak Kuzu

Amaç: Dünya çapında en çok ölüme neden olan kardiyovasküler hastalık iskemik kalp hastalığıdır. Değiştirilebilir ve değiştirilemez risk faktörlerinin yanı sıra, özellikle ağır metaller olmak üzere çevresel faktörlerin de iskemik kalp hastalığı riskine katkıda bulunabileceği düşünülmektedir. Çalışmamızın amacı, arsenik, kadmiyum, kurşun ve cıva tarafından indüklenen iskemik kalp hastalığı ile ilişkilendirilebilecek potansiyel moleküler mekanizmaları belirlemektir.

Gereç ve Yöntem: Bu çalışmada toksikogenomik verileri ve Comparative Toxicogenomic Database, ToppGene Suite, GeneMANIA, STRING, Cytoscape, ChEA3 ve MIENTURNET gibi biyoinformatik veritabanlarını ve araçları kullandık.

Bulgular: Çalışılan metaller ve iskemik kalp hastalığı ile ilişkili genlerden CRP, HMOX1, PON1 ve PTGS2’nin örtüştüğünü gözlemledik. Bu örtüşen genler arasında en yaygın etkileşim fiziksel etkileşimdi (%77,64). Çalışılan metallerin etkileyebilecekleri temel moleküler mekanizmalar olarak çeşitli yolaklar tanımlandı ve bunlar, iskemik kalp hastalığının etiyolojisinde rol oynayan yolakları içeriyordu (örneğin, plazma lipoprotein parçacık seviye lerinin düzenlenmesi, inorganik maddelere yanıt, kan dolaşımı, dolaşım sistemi süreçleri ve metal iyonlarına hücresel yanıt). Bu metallerin indük lediği iskemik kalp hastalığı ile ilişkili olarak temel genler CRP ve HMOX1 iken, ATF5 ve CREB3L3 de temel transkripsiyon faktörleri olarak belirlendi. Ayrıca, iskemik kalp hastalığıyla ilişkili iki miRNA da (hsa-miR-128-3p ve hsa-miR-1273g-3p) belirledik.

Sonuç: Bu gözlemler arsenik, kadmiyum, kurşun ve cıvanın neden olduğu iskemik kalp hastalığının altında yatan süreçleri anlamamıza önemli bir katkı sağlamaktadır.


PDF View

References

  • Duggan JP, Peters AS, Trachiotis GD, Antevil JL. Epidemiology of coronary artery disease. Surg Clin North Am 2022;102(3):499-516. google scholar
  • Malakar AK, Choudhury D, Halder B, Paul P, Uddin A, Chakraborty S. A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol 2019;234(10):16812-23. google scholar
  • Chen Z, Huo X, Chen G, Luo X, Xu X. Lead (Pb) exposure and heart failure risk. Environ Sci Pollut Res Int 2021;28(23):28833-47. google scholar
  • Wang Z, Xue K, Wang Z, Zhu X, Guo C, Qian Y, et al. Effects of e-waste exposure on biomarkers of coronary heart disease (CHD) and their associations with level of heavy metals in blood. Environ Sci Pollut Res Int 2022;29(33):49850-7. google scholar
  • Gump BB, Heffernan K, Brann LS, Hill DT, Labrie-Cleary C, Jandev V et al. Exposure to arsenic and subclinical cardiovascular disease in 9- to 11-year-old children, syracuse, new york. JAMA Netw Open 2023;6(6):e2321379. google scholar
  • Das S, Sultana KW, Ndhlala AR, Mondal M, Chandra I. Heavy metal pollution in the environment and its impact on health: exploring green technology for remediation. Environ Health Insights 2023;17:11786302231201259. google scholar
  • Xu L, Mondal D, Polya DA. Positive association of cardiovascular disease with chronic exposure to drinking water arsenic at concentrations below the who provisional guideline value: a systematic review and meta-Analysis. Int J Environ Res Public Health 2020;17(7):2536. google scholar
  • Glicklich D, Shin CT, Frishman WH. Heavy metal toxicity in chronic renal failure and cardiovascular disease: possible role for chelation therapy. Cardiol Rev 2020;28(6):312-8. google scholar
  • Hu XF, Lowe M, Chan HM. Mercury exposure, cardiovascular disease, and mortality: a systematic review and dose-response meta-analysis. Environ Res 2021;193:110538. google scholar
  • Tsuji JS, Perez V, Garry MR, Alexander DD. Association of low-level arsenic exposure in drinking water with cardiovascular disease: a systematic review and risk assessment. Toxicology 2014;323:78-94. google scholar
  • Ujueta F, Navas-Acien A, Mann KK, Prashad R, Lamas GA. Low-level metal contamination and chelation in cardiovascular disease-a ripe area for toxicology research. Toxicol Sci 2021;181(2):135-47. google scholar
  • Nigra AE, Moon KA, Jones MR, Sanchez TR, Navas-Acien A. Urinary arsenic and heart disease mortality in nhanes 2003-2014. Environ Res 2021;200:111387. google scholar
  • Liu J, Song W, Li Y, Wang Y, Cui Y, Huang J, et al. Burden of coronary heart disease and cancer from dietary exposure to inorganic arsenic in adults in china, 2016. Ann Glob Health 2022;88(1):28. google scholar
  • Liu J, Li Y, Li D, Wang Y, Wei S. The burden of coronary heart disease and stroke attributable to dietary cadmium exposure in chinese adults, 2017. Sci Total Environ 2022;825:153997. google scholar
  • Davis AP, Wiegers TC, Johnson RJ, Sciaky D, Wiegers J, Mattingly CJ. Comparative toxicogenomics database (ctd): update 2023. Nucleic Acids Res 2023;51(D1):D1257-62. google scholar
  • Sun L, Dong S, Ge Y, Fonseca JP, Robinson ZT, Mysore KS, Mehta P. Divenn: an interactive and integrated web-based visualization tool for comparing gene lists. Front Genet 2019;10:421. google scholar
  • Chen J, Bardes EE, Aronow BJ, Jegga AG. Toppgene suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 2009;37:W305-W311. google scholar
  • Franz M, Rodriguez H, Lopes C, Zuberi K, Montojo J, Bader GD, et al. Genemania update 2018. Nucleic Acids Res 2018;46(W1):W60-W64. google scholar
  • Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, et al. The string database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res 2023;51(D1):D638-D646. google scholar
  • Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003;13(11):2498-2504. google scholar
  • Keenan AB, Torre D, Lachmann A, Leong AK, Wojciechowicz ML, Utti V, et al. Chea3: transcription factor enrichment analysis by orthogonal omics integration. Nucleic Acids Res 2019;47(W1):W212-W224. google scholar
  • Licursi V, Conte F, Fiscon G, Paci P. Mienturnet: an interactive web tool for microrna-target enrichment and network-based analysis. BMC Bioinform 2019;20(1):545. google scholar
  • Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010;375(9709):132-40. google scholar
  • Ridker PM. From c-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res 2016;118(1):145-56. google scholar
  • Amezcua-Castillo E, Gonzâlez-Pacheco H, Sâenz-San Martm A, Mendez-Ocampo P, Gutierrez-Moctezuma I, Masso F, et al. C-Reactive Protein: The quintessential marker of systemic inflammation in coronary artery disease-advancing toward precision medicine. Biomedicines 2023;11(9):2444. google scholar
  • Jozkowicz A, Was H, Dulak J. Heme oxygenase-1 in tumors: is it a false friend? Antioxid Redox Signal 2007;9(12):2099-117. google scholar
  • Otterbein LE, Foresti R, Motterlini R. Heme oxygenase-1 and carbon monoxide in the heart: the balancing act between danger signaling and pro-survival. Circ Res 2016;118(12):1940-59. google scholar
  • Nguyen HD, Kim MS. Effects of heavy metals on cardiovascular diseases in pre and post-menopausal women: from big data to molecular mechanism involved. Environ Sci Pollut Res Int 2022;29(51):77635-55. google scholar
  • Nakagawa Y, Wang Y, Han SI, Okuda K, Oishi A, Yagishita Y, et al. Enterohepatic transcription factor creb3L3 protects atherosclerosis via srebp competitive inhibition. Cell Mol Gastroenterol Hepatol 2021;11(4):949-71. google scholar
  • Chen GH, Xu CS, Zhang J, Li Q, Cui HH, Li XD, et al. Inhibition of mir-128-3p by tongxinluo protects human cardiomyocytes from ischemia/reperfusion injury via upregulation of p70s6k1/p-p70s6k1. Front Pharmacol 2017;8:775. google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Karakuş, F., & Kuzu, B. (2024). LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS. Journal of Advanced Research in Health Sciences, 7(3), 201-208. https://doi.org/10.26650/JARHS2024-1397075


AMA

Karakuş F, Kuzu B. LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS. Journal of Advanced Research in Health Sciences. 2024;7(3):201-208. https://doi.org/10.26650/JARHS2024-1397075


ABNT

Karakuş, F.; Kuzu, B. LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS. Journal of Advanced Research in Health Sciences, [Publisher Location], v. 7, n. 3, p. 201-208, 2024.


Chicago: Author-Date Style

Karakuş, Fuat, and Burak Kuzu. 2024. “LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS.” Journal of Advanced Research in Health Sciences 7, no. 3: 201-208. https://doi.org/10.26650/JARHS2024-1397075


Chicago: Humanities Style

Karakuş, Fuat, and Burak Kuzu. LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS.” Journal of Advanced Research in Health Sciences 7, no. 3 (Dec. 2024): 201-208. https://doi.org/10.26650/JARHS2024-1397075


Harvard: Australian Style

Karakuş, F & Kuzu, B 2024, 'LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS', Journal of Advanced Research in Health Sciences, vol. 7, no. 3, pp. 201-208, viewed 22 Dec. 2024, https://doi.org/10.26650/JARHS2024-1397075


Harvard: Author-Date Style

Karakuş, F. and Kuzu, B. (2024) ‘LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS’, Journal of Advanced Research in Health Sciences, 7(3), pp. 201-208. https://doi.org/10.26650/JARHS2024-1397075 (22 Dec. 2024).


MLA

Karakuş, Fuat, and Burak Kuzu. LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS.” Journal of Advanced Research in Health Sciences, vol. 7, no. 3, 2024, pp. 201-208. [Database Container], https://doi.org/10.26650/JARHS2024-1397075


Vancouver

Karakuş F, Kuzu B. LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS. Journal of Advanced Research in Health Sciences [Internet]. 22 Dec. 2024 [cited 22 Dec. 2024];7(3):201-208. Available from: https://doi.org/10.26650/JARHS2024-1397075 doi: 10.26650/JARHS2024-1397075


ISNAD

Karakuş, Fuat - Kuzu, Burak. LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS”. Journal of Advanced Research in Health Sciences 7/3 (Dec. 2024): 201-208. https://doi.org/10.26650/JARHS2024-1397075



TIMELINE


Submitted28.11.2023
Accepted19.04.2024
Published Online01.10.2024

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.