LINKING METAL EXPOSURE TO ISCHAEMIC HEART DISEASE: A BIOINFORMATIC ANALYSIS

Abstract

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.

Keywords

• Ischaemic heart disease
• arsenic
• cadmium
• lead
• mercury
• big data

METAL MARUZİYETİNİN İSKEMİ KALP HASTALIĞIYLA BAĞLANTISI: BİYOİNFORMATİK ANALİZ

Abstract

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.

Keywords

• İskemik kalp hastalığı
• arsenik
• kadmiyum
• kurşun
• cıva
• büyük veri

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