Post-COVID-19 Cardiovascular Disorders and the Molecular Mechanism of NET Formation

Year 2023, , 302 - 307, 20.10.2023

Lütfiye Özpak , Ekrem Aksu , İbrahim Seyfettin Çelik , Bekir Mehmet Kelleci , Mustafa Çelik , Celal Kuş

https://doi.org/10.18521/ktd.1323455

Abstract

Objective: The post-COVID-19 process is not completely understood, as it affects COVID-19 survivors at all levels of disease severity, not all of whom are hospitalized. One of the long-lasting COVID-19 symptom categories, cardiovascular disorders (including acute heart failure, palpitations, hypotension, venous thromboembolic diseases, arrhythmias, myocarditis, and increased heart rate), may derive from a systemic inflammatory response to the viral infection. NETs (neutrophil extracellular traps) that fight invading viruses in extracellular cardiac spaces accumulate due to COVID-19, hyperinflammation and cytokine storms. Our study focuses on cardiovascular disorders as COVID-19 sequelae. To determine the role of NETs in these disorders, we aimed to measure levels of PAD4, MPO, MMP-9, and H3Cit. Methods: In this study, forty people with long-term cardiac complications associated with a history of COVID-19 were recruited along with forty healthy people. Results: We found significant differences in PAD4, H3Cit, and MPO plasma levels between the post-COVID-19 and control groups (p values < 0.05). The expression levels of PAD4 mRNA were lower and MMP-9 mRNA levels was higher in the post-COVID-19 group compared with the control subjects. Conclusion: These findings suggest that PAD4, MPO, MMP-9, and H3Cit are potential biomarkers of NET dysregulation and may cause post-COVID-19 symptoms, especially cardiovascular disorders.

Keywords

Cardiovascular abnormalities, citrullinated Histone H3, neutrophil extracellular traps, peptidylarginine deiminases 4, post-acute COVID-19 syndrome.

Project Number

2021/2-33 M.

COVID-19 Sonrası Kardiyovasküler Bozukluklar ve NET Oluşumunun Moleküler Mekanizması

Abstract

Amaç: COVID-19 sonrası süreç, tamamı hastaneye yatırılmayan, hastalık şiddetinin her seviyesindeki COVID-19 mağdurlarını etkilediği için tam olarak anlaşılamamıştır. Uzun süreli COVID-19 semptom kategorilerinden biri olan kardiyovasküler bozukluklar (akut kalp yetmezliği, çarpıntı, hipotansiyon, venöz tromboembolik hastalıklar, aritmiler, miyokardit ve artmış kalp hızı dahil), viral enfeksiyona sistemik bir inflamatuar yanıttan kaynaklanabilir. Hücre dışı kalp boşluklarında istilacı virüslerle savaşan NET'ler (nötrofil hücre dışı tuzakları), COVID-19, hiperinflamasyon ve sitokin fırtınaları nedeniyle birikir. Çalışmamız, COVID-19 sekeli olarak kardiyovasküler bozukluklara odaklanmaktadır. NET'lerin bu bozukluklardaki rolünü belirlemek için PAD4, MPO, MMP-9 ve H3Cit düzeylerini ölçmeyi amaçladık. Yöntemler: Bu çalışmada, COVID-19 öyküsü ile ilişkili uzun süreli kardiyak komplikasyonları olan kırk sağlıklı insanla birlikte çalışmaya alındı. Bulgular: COVID-19 sonrası ve kontrol grupları arasında PAD4, H3Cit ve MPO plazma seviyelerinde anlamlı farklılıklar bulduk (p değerleri < 0,05). PAD4 mRNA'nın ekspresyon seviyeleri, kontrol deneklerine kıyasla COVID-19 sonrası grupta daha düşük ve MMP-9 mRNA seviyeleri daha yüksekti. Sonuç: Bu bulgular, PAD4, MPO, MMP-9 ve H3Cit'in NET düzensizliğinin potansiyel biyobelirteçleri olduğunu ve özellikle kardiyovasküler bozukluklar olmak üzere COVID-19 sonrası semptomlara neden olabileceğini düşündürmektedir.

Keywords

Kardiyovasküler anormallikler, sitrüline Histon H3, nötrofil hücre dışı tuzakları, peptidilarjinin deiminazlar 4, Post akut COVID-19 sendromu

Supporting Institution

Kahramanmaraş Sütçü İmam Üniversitesi Bilimsel Araştırma Projeleri Birimi

Project Number

2021/2-33 M.

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