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Expression level of the angiotensin 2 (ACE2) gene in patients with COVID-19

Year 2021, Volume: 46 Issue: 4, 1508 - 1515, 30.12.2021
https://doi.org/10.17826/cumj.982658

Abstract

Purpose: Coronavirus disease -19 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV2). The angiotensin converting enzyme 2 (ACE2) can play a vital role in regulating the pathological changes of various diseases, including COVID-19. The aim of this study was to analyze the expression of the ACE2 gene in Turkish COVID-19 patients.
Materials and Methods: Eighty COVID-19 PCR test positive patients and 80 PCR test negative healthy volunteers were included in the study. RNA isolation was carried out from all samples. The RT-PCR device was used to analyze the expression of the ACE2 gene.
Results: A significant difference was found in the age, Lactate dehydrogenase (LDH), ferritin and C-reactive protein (CRP) levels of the COVID-19 patients compared to the healthy volunteers. Based on the gene expression results, it was found that ACE2 gene expression was significantly higher in COVID-19 patients compared to healthy volunteers. In patients with COVID-19, a significant difference was found between the expression of the ACE2 gene and the levels of Blood urea nitrogen (BUN), Hemoglobin (HGB), Hematocrit (HCT) and CRP.
Conclusion: ACE2 gene expression was high in the COVID-19 patients and showed differences based on clinical data. Thus, the expression of ACE2 can have paradoxical effects that support the pathogenicity of SARSCoV2 but, conversely, limit viral infection. The availability of ACE2 receptors may increase the susceptibility and / or disease course of COVID-19.

References

  • 1. Gül Ü. COVID-19 and dermatology. TURKISH J Med Sci. 2020;50(8):1751–9.
  • 2. Scialo F, Daniele A, Amato F, et al. ACE2: The Major Cell Entry Receptor for SARS-CoV-2. Lung. 2020;198(6):867–77.
  • 3. Wiese O, Zemlin AE, Pillay TS. Molecules in pathogenesis: angiotensin converting enzyme 2 (ACE2). J Clin Pathol. 2021;74(5):285–90.
  • 4. Yamamoto K, Takeshita H, Rakugi H. ACE2, angiotensin 1-7 and skeletal muscle: review in the era of COVID-19. Clin Sci. 2020;134(22):3047–62.
  • 5. Beacon TH, Delcuve GP, Davie JR. Epigenetic regulation of ACE2, the receptor of the SARS-CoV-2 virus 1. Genome. 2021;64(4):386–99.
  • 6. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–33.
  • 7. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-280.e8.
  • 8. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science (80- ). 2020;367(6485):1444–8.
  • 9. Kowalczuk S, Bröer A, Tietze N, Vanslambrouck JM, Rasko JEJ, Bröer S. A protein complex in the brush‐border membrane explains a Hartnup disorder allele. FASEB J. 2008;22(8):2880–7.
  • 10. Lin Q, Keller RS, Weaver B, Zisman LS. Interaction of ACE2 and integrin β1 in failing human heart. Biochim Biophys Acta - Mol Basis Dis. 2004;1689(3):175–8.
  • 11. Gholizadeh P, Safari R, Marofi P, et al. Alteration of Liver Biomarkers in Patients with SARS-CoV-2 (COVID-19). J Inflamm Res. 2020;Volume 13:285–92. 12. Guan W, Ni Z, Hu YYY, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708–20.
  • 13. Bunyavanich S, Do A, Vicencio A. Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults. JAMA. 2020;323(23):2427.
  • 14. Patel AB, Verma A. Nasal ACE2 Levels and COVID-19 in Children. JAMA. 2020;323(23):2386.
  • 15. Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):8.
  • 16. Smith JC, Sausville EL, Girish V, et al. Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract. Dev Cell. 2020;53(5):514-529.e3.
  • 17. Ishiyama Y, Gallagher PE, Averill DB, Tallant EA, Brosnihan KB, Ferrario CM. Upregulation of Angiotensin-Converting Enzyme 2 After Myocardial Infarction by Blockade of Angiotensin II Receptors. Hypertension. 2004;43(5):970–6.
  • 18. Wang X, Ye Y, Gong H, et al. The effects of different angiotensin II type 1 receptor blockers on the regulation of the ACE-AngII-AT1 and ACE2-Ang(1–7)-Mas axes in pressure overload-induced cardiac remodeling in male mice. J Mol Cell Cardiol. 2016;97:180–90.
  • 19. Chai X et al., Chai X, Hu L, et al. Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection. BioRxiv. 2020.
  • 20. Kragstrup TW, Singh HS, Grundberg I, et al. Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients. PLoS One. 2021;16(6):e0252799.
  • 21. Narula S, Yusuf S, Chong M, et al. Plasma ACE2 and risk of death or cardiometabolic diseases: a case-cohort analysis. Lancet (London, England). 2020;396(10256):968–76.
  • 22. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020.
  • 23. Zhang W, Zhao Y, Zhang F, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The experience of clinical immunologists from China. Clin Immunol. 2020.

COVID-19 hastalarında anjiyotensin 2 (ACE2) genin ekspresyon seviyesi

Year 2021, Volume: 46 Issue: 4, 1508 - 1515, 30.12.2021
https://doi.org/10.17826/cumj.982658

Abstract

Amaç: Coronavirus hastalığı-19 (COVID-19), şiddetli akut solunum sendromu koronavirüs 2'den (SARS-CoV-2) kaynaklanır. Anjiyotensin dönüştürücü enzim 2 (ACE2), COVID-19 dahil olmak üzere çeşitli hastalıkların patolojik değişikliklerini düzenlemede hayati bir rol oynayabilir. Bu çalışmanın amacı ACE2 genin ekspresyonunu Türk COVID-19 hastalarında analiz etmekti.
Gereç ve Yöntem: Bu çalışmada 80 COVID-19 PCR testi pozitif hasta ve 80 PCR testi negatif olan sağlıklı gönüllü birey çalışmaya dahil edildi. Tüm örneklerden RNA izolasyonu yapıldı. ACE2 geninin ekspresyonunu analiz etmek için RT-PZR cihazı kullanıldı.
Bulgular: COVID-19 hastalarının yaş, Laktat dehidrojenaz (LDH), ferritin ve C-reaktif protein (CRP) seviyelerinde sağlıklı gönüllülere kıyasla anlamlı bir fark bulundu. Gen ekspresyon sonuçlarına göre, ACE2 geni ekspresyonu COVID-19 hastalarında sağlıklı gönüllülere kıyasla anlamlı derecede yüksek bulundu. COVID-19 hastalarında ACE2 geninin ekspresyonu ile Kan üre nitrojeni (BUN), Hemoglobin (HGB), Hematokrit (HCT) ve CRP seviyeleri arasında anlamlı bir fark bulundu.
Sonuç: ACE2 gen ekspresyonu COVID-19 hastalarında yüksek bulundu ve klinik verilere göre farklılıklar gösterdi. Bu nedenle, ACE2'nin ekspresyonu, SARSCoV2'nin patojenitesini destekleyen ancak tersine viral enfeksiyonu sınırlayan paradoksal etkilere sahip olabilir. ACE2 reseptörlerinin mevcudiyeti, COVID-19'un duyarlılığını ve/veya hastalık seyrini artırabilir.

References

  • 1. Gül Ü. COVID-19 and dermatology. TURKISH J Med Sci. 2020;50(8):1751–9.
  • 2. Scialo F, Daniele A, Amato F, et al. ACE2: The Major Cell Entry Receptor for SARS-CoV-2. Lung. 2020;198(6):867–77.
  • 3. Wiese O, Zemlin AE, Pillay TS. Molecules in pathogenesis: angiotensin converting enzyme 2 (ACE2). J Clin Pathol. 2021;74(5):285–90.
  • 4. Yamamoto K, Takeshita H, Rakugi H. ACE2, angiotensin 1-7 and skeletal muscle: review in the era of COVID-19. Clin Sci. 2020;134(22):3047–62.
  • 5. Beacon TH, Delcuve GP, Davie JR. Epigenetic regulation of ACE2, the receptor of the SARS-CoV-2 virus 1. Genome. 2021;64(4):386–99.
  • 6. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–33.
  • 7. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-280.e8.
  • 8. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science (80- ). 2020;367(6485):1444–8.
  • 9. Kowalczuk S, Bröer A, Tietze N, Vanslambrouck JM, Rasko JEJ, Bröer S. A protein complex in the brush‐border membrane explains a Hartnup disorder allele. FASEB J. 2008;22(8):2880–7.
  • 10. Lin Q, Keller RS, Weaver B, Zisman LS. Interaction of ACE2 and integrin β1 in failing human heart. Biochim Biophys Acta - Mol Basis Dis. 2004;1689(3):175–8.
  • 11. Gholizadeh P, Safari R, Marofi P, et al. Alteration of Liver Biomarkers in Patients with SARS-CoV-2 (COVID-19). J Inflamm Res. 2020;Volume 13:285–92. 12. Guan W, Ni Z, Hu YYY, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708–20.
  • 13. Bunyavanich S, Do A, Vicencio A. Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults. JAMA. 2020;323(23):2427.
  • 14. Patel AB, Verma A. Nasal ACE2 Levels and COVID-19 in Children. JAMA. 2020;323(23):2386.
  • 15. Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):8.
  • 16. Smith JC, Sausville EL, Girish V, et al. Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract. Dev Cell. 2020;53(5):514-529.e3.
  • 17. Ishiyama Y, Gallagher PE, Averill DB, Tallant EA, Brosnihan KB, Ferrario CM. Upregulation of Angiotensin-Converting Enzyme 2 After Myocardial Infarction by Blockade of Angiotensin II Receptors. Hypertension. 2004;43(5):970–6.
  • 18. Wang X, Ye Y, Gong H, et al. The effects of different angiotensin II type 1 receptor blockers on the regulation of the ACE-AngII-AT1 and ACE2-Ang(1–7)-Mas axes in pressure overload-induced cardiac remodeling in male mice. J Mol Cell Cardiol. 2016;97:180–90.
  • 19. Chai X et al., Chai X, Hu L, et al. Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection. BioRxiv. 2020.
  • 20. Kragstrup TW, Singh HS, Grundberg I, et al. Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients. PLoS One. 2021;16(6):e0252799.
  • 21. Narula S, Yusuf S, Chong M, et al. Plasma ACE2 and risk of death or cardiometabolic diseases: a case-cohort analysis. Lancet (London, England). 2020;396(10256):968–76.
  • 22. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020.
  • 23. Zhang W, Zhao Y, Zhang F, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The experience of clinical immunologists from China. Clin Immunol. 2020.
There are 22 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research
Authors

Ebubekir Dirican 0000-0001-9260-5223

İsmail Erkan Aydın 0000-0003-3552-5459

Şeyda Savrun 0000-0002-6512-2987

Publication Date December 30, 2021
Acceptance Date September 25, 2021
Published in Issue Year 2021 Volume: 46 Issue: 4

Cite

MLA Dirican, Ebubekir et al. “COVID-19 hastalarında Anjiyotensin 2 (ACE2) Genin Ekspresyon Seviyesi”. Cukurova Medical Journal, vol. 46, no. 4, 2021, pp. 1508-15, doi:10.17826/cumj.982658.