COVID-19 hastalarında serum adropin düzeylerinin dolaşımdaki endotel disfonksiyon biyobelirteçleri üzerine etkisi
Abstract
Amaç: Çalışmalar, şiddetli COVID-19 enfeksiyonu semptomlarının endotel disfonksiyonunun klinik fenotipini yansıttığını ve endotel disfonksiyonuyla ortak patofizyolojik mekanizmalar paylaştığını göstermektedir. Bu nedenle çalışmamızda, serum adropin düzeylerinin endotelyal disfonksiyon biyobelirteçleri üzerindeki etkisini ve adropinin COVID-19 için yeni bir biyobelirteç olup olamayacağını araştırmayı amaçladık.
Gereç ve Yöntem: Çalışmaya 40 hafif/orta semptomlu, 48 ağır/kritik semptomlu COVID-19 hastası ve 37 kontrol dahil edilmiştir. Serum adropin ve asimetrik dimetilarginin (ADMA), endotelin-1 (ET-1), endotelyal nitrik oksit sentaz (eNOS), çözünür hücrelerarası adezyon molekülü-1 (sICAM-1) ve plazminojen aktivatör inhibitörü-1 (PAI-1) gibi endotelyal disfonksiyon biyobelirteçlerinin serum seviyeleri mikro-ELISA yöntemiyle belirlendi.
Bulgular: COVID-19 hastalarında serum adropin düzeyleri (165.2±11.49 pg/ml), kontrol grubuna (85.46±12.08 pg/ml) göre anlamlı derecede yüksek bulundu. Şiddetli/kritik semptomları olan hastaların serum adropin düzeyleri (194±16.23 pg/ml), hafif/orta semptomları olan hastalardan (130.6 ±14.53) anlamlı derecede yüksekti. Ayrıca, COVID-19 olgularında serum ADMA, eNOS ve ET-1 düzeyleri (sırasıyla; 150.5±8.67 ng/ml, 172.4±14.01 pg/ml, 159.3±10.19 pg/ml) kontrollere göre (sırasıyla; 104.5±9.182 ng/ml, 141.4±17.74 pg/ml, 100.1±11.37 pg/ml) anlamlı derecede yüksek bulundu. Hastalarda, adropin ile ADMA, eNOS, ET-1, sICAM-1 ve PAI-1 düzeyleri arasında anlamlı pozitif korelasyonlar saptandı.
Sonuç: Bulgularımız, adropinin COVID-19 için yeni bir potansiyel biyobelirteç ve endotel hücre hasarının onarımında önemli bir molekül olabileceğini göstermektedir. Hastalarda serum adropin düzeyleri ile ADMA, eNOS, ET-1, sICAM-1 ve PAI-1 seviyeleri arasındaki pozitif korelasyonlar, adropinin endotel hücrelerindeki hasarı telafi edebileceğini düşündürmektedir.
Supporting Institution
Alanya Alaaddin Keykubat Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi
Project Number
2021-04-01-MAP13
Thanks
Projemizi destekleyen Alanya Alaaddin Keykubat Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi'ne ve çalışmamıza katılan gönüllülere teşekkür ederiz.
References
- Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA. Chouljenko VN et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. 2008;8:468-81.
- Lovren F, Pan Y, Quan A,. Singh KK, Shukla PC, Gupta M et al. Adropin is a novel regulator of endothelial function. Circulation. 2010;122:185-92.
- Butler AA, Tam CS, Stanhope KL, Wolfe BM, Ali MR, O'Keeffe M et al. Low circulating adropin concentrations with obesity and aging correlate with risk factors for metabolic disease and increase after gastric bypass surgery in humans. J Clin Endocrinol Metab. 2012;97:3783-91.
- Topuz M, Celik A, Aslantas T, Demir AK, Aydin S, Aydin S. Plasma adropin levels predict endothelial dysfunction like flow-mediated dilatation in patients with type 2 diabetes mellitus. J Investig Med. 2013;61:1161-4.
- Celik A, Balin M, Kobat M.A, Erdem K, Baydas A, Bulut M et al. Deficiency of a new protein associated with cardiac syndrome X; called adropin. Cardiovasc Ther. 2013;31:174-8.
- Gu X, Li H, Zhu X, Gu H, Chen J, Wang L et al. Inverse correlation between plasma adropin and ET-1 levels in essential hypertension: A cross-sectional study. Medicine (Baltimore). 2015;94:e1712.
- Yau, JW, Teoh H, Verma S. Endothelial cell control of thrombosis. BMC Cardiovasc Disord. 2015;15:130.
- Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395:1417-8.
- Steinberg BE, Goldenberg NM, Lee WL. Do viral infections mimic bacterial sepsis? The role of microvascular permeability: A review of mechanisms and methods, Antiviral Res. 2012;93:2-15.
- Goeijenbier M, van Wissen M, van de Weg C, Jong E, Gerdes VE, Meijers JC et al. Review: Viral infections and mechanisms of thrombosis and bleeding. J Med Virol. 2012;84:1680-96.
- National Institutes of Health. Clinical spectrum of SARS-CoV-2 infection. https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/ (accessed Jan 2022).
- Serebrovska ZO, Chong EY, Serebrovska TV, Tumanovska LV, Xi L. Hypoxia, HIF-1α, and COVID-19: from pathogenic factors to potential therapeutic targets. Acta Pharmacol Sin. 2020;41:1539–46.
- Kurt E, Tekin E, Kurt N, Bayramoglu A. The role of adropin, HIF-1α and apelin biomarkers in the diagnosis of acute mesentaric ischemia. Am J Emerg Med. 2022;51:223-27.
- Prasad M, Leon M, Lerman LO, Lerman A. Viral endothelial dysfunction: A unifying mechanism for COVID-19. Mayo Clin Proc. 2021;96:3099-108.
- Aydın P, Karabulut Uzunçakmak S ,Tör IH , Bilen A , Özden A. Comparison of serum adropin levels in patients with diabetes mellitus, COVID-19, and COVID-19 with diabetes mellitus. Eurasian J Med. 2022;54:197-201.
- Goshua G, Pine AB, Meizlish ML, Chang CH, Zhang H, Bahel P et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020;7:e575-82.
- Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol. 2000;20:2032-7.
- Hannemann J, Balfanz P, Schwedhelm E, Hartmann B, Ule J, Müller-Wieland D et al. Elevated serum SDMA and ADMA at hospital admission predict in-hospital mortality of COVID-19 patients. Sci Rep. 2021;11:9895.
- Emlek N, Yilmaz AS, Ergul E, Gundogdu H, Arpa M, Koc H, et al. The relationship of serum asymmetric dimethylarginine concentrations and lung involvement in patients with COVID-19 infection. Exp Biomed Res. 2021;4:314-21.
- Farhangrazi, Shadi Z, Moghimi SM. Elevated circulating endothelin-1 as a potential biomarker for high-risk COVID-19 severity. Precis Nanomed. 2020;3:622-28.
- Abraham GR, Kuc RE, Althage M, Greasley PJ, Ambery P, Maguire JJ et al. Endothelin-1 is increased in the plasma of patients hospitalized with Covid-19. J Mol Cell Cardiol. 2022;167:92-6.
- Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012:33:829-37.
- Guan SP, Seet RCS, Kennedy BK. Does eNOS derived nitric oxide protect the young from severe COVID-19 complications? Ageing Res Rev. 2020;64:101201.
- Green SJ. Covid-19 accelerates endothelial dysfunction and nitric oxide deficiency. Microbes Infect. 2020;22:149-50.
- Tong M, Jiang Y, Xia D, Xiong Y, Zheng Q, Chen F et al. Elevated expression of serum endothelial cell adhesion molecules in COVID-19 patients. J Infect Dis. 2020;222:894–8.
- Vassiliou AG, Keskinidou C, Jahaj E, Gallos P, Dimopoulou I, Kotanidou A et al. ICU admission levels of endothelial biomarkers as predictors of mortality in critically Ill COVID-19 patients. Cells. 2021;10:186.
- Dellas C, Loskutoff DJ. Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost. 2005;93:631-40.
- Vaughan DE. PAI-1 and atherothrombosis. J Thromb Haemost. 2005;3:1879-83.
- Baluta MM, Vintila MM. PAI-1 inhibition - another therapeutic option for cardiovascular protection. Maedica (Bucur). 2015;10:147-52.
- Ranucci M, Ballotta A, Di Dedda U, Bayshnikova E, Dei Poli M, Resta M et al. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost. 2020;18:1747-51.
- Masi P, Hekimian G, Lejeune M, Chommeloux J, Desnos C, De Chambrun MP et al. Systemic inflammatory response syndrome is a major contributor to COVID-19-associated coagulopathy: Insights from a prospective, single-center cohort study. Circulation. 2020;142:611-4.
- Zuo Y, Warnock M, Harbaugh A, Yalavarthi S, Gockman K, Zuo M et al. Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients. Sci Rep. 2021;11:1580.
Effect of serum adropin levels on circulating endothelial dysfunction biomarkers in COVID-19 patients
Abstract
Purpose: Several studies show that the symptoms of severe COVID-19 infection reflect the clinical phenotype of endothelial dysfunction and share common pathophysiological mechanisms with endothelial dysfunction. Therefore, the aim of the study was to investigate the effect of serum adropin levels on endothelial dysfunction biomarkers and determine whether adropin could be a new biomarker for COVID-19.
Materials and Methods: The study included 40 patients with mild/moderate COVID-19, 48 patients with severe/critical COVID-19, and 37 controls. Serum adropin and circulating biomarkers of endothelial dysfunction including asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble intercellular adhesion molecule-1 (sICAM-1) and plasminogen activator inhibitor-1 (PAI-1) levels were determined by micro-ELISA.
Results: Serum adropin levels were found to be significantly higher in COVID-19 patients (165.2±11.49 pg/ml) than in controls (85.46±12.08 pg/ml). Serum adropin levels of patients with severe/critical symptoms (194±16.23 pg/ml) were significantly higher than the patients with mild/moderate symptoms (130.6 ±14.53). In addition, serum ADMA, eNOS, and, ET-1 levels were significantly higher in the COVID-19 subjects (150.5±8.67 ng/ml, 172.4±14.01 pg/ml, 159.3±10.19 pg/ml, respectively) than that those in the controls (104.5±9.182 ng/ml, 141.4±17.74 pg/ml, 100.1±11.37 pg/ml, respectively). Significant positive correlations were found between adropin and ADMA, eNOS, ET-1, sICAM-1, and PAI-1 levels in the patients.
Conclusion: We suggest that adropin may be a new potential biomarker for COVID-19 and an important molecule in restoring endothelial cell damage. Positive correlations between serum adropin levels and ADMA, eNOS, ET-1, sICAM-1 and PAI-1 levels in patients suggest that adropin may compensate for damage to endothelial cells.
Project Number
2021-04-01-MAP13
References
- Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA. Chouljenko VN et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. 2008;8:468-81.
- Lovren F, Pan Y, Quan A,. Singh KK, Shukla PC, Gupta M et al. Adropin is a novel regulator of endothelial function. Circulation. 2010;122:185-92.
- Butler AA, Tam CS, Stanhope KL, Wolfe BM, Ali MR, O'Keeffe M et al. Low circulating adropin concentrations with obesity and aging correlate with risk factors for metabolic disease and increase after gastric bypass surgery in humans. J Clin Endocrinol Metab. 2012;97:3783-91.
- Topuz M, Celik A, Aslantas T, Demir AK, Aydin S, Aydin S. Plasma adropin levels predict endothelial dysfunction like flow-mediated dilatation in patients with type 2 diabetes mellitus. J Investig Med. 2013;61:1161-4.
- Celik A, Balin M, Kobat M.A, Erdem K, Baydas A, Bulut M et al. Deficiency of a new protein associated with cardiac syndrome X; called adropin. Cardiovasc Ther. 2013;31:174-8.
- Gu X, Li H, Zhu X, Gu H, Chen J, Wang L et al. Inverse correlation between plasma adropin and ET-1 levels in essential hypertension: A cross-sectional study. Medicine (Baltimore). 2015;94:e1712.
- Yau, JW, Teoh H, Verma S. Endothelial cell control of thrombosis. BMC Cardiovasc Disord. 2015;15:130.
- Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395:1417-8.
- Steinberg BE, Goldenberg NM, Lee WL. Do viral infections mimic bacterial sepsis? The role of microvascular permeability: A review of mechanisms and methods, Antiviral Res. 2012;93:2-15.
- Goeijenbier M, van Wissen M, van de Weg C, Jong E, Gerdes VE, Meijers JC et al. Review: Viral infections and mechanisms of thrombosis and bleeding. J Med Virol. 2012;84:1680-96.
- National Institutes of Health. Clinical spectrum of SARS-CoV-2 infection. https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/ (accessed Jan 2022).
- Serebrovska ZO, Chong EY, Serebrovska TV, Tumanovska LV, Xi L. Hypoxia, HIF-1α, and COVID-19: from pathogenic factors to potential therapeutic targets. Acta Pharmacol Sin. 2020;41:1539–46.
- Kurt E, Tekin E, Kurt N, Bayramoglu A. The role of adropin, HIF-1α and apelin biomarkers in the diagnosis of acute mesentaric ischemia. Am J Emerg Med. 2022;51:223-27.
- Prasad M, Leon M, Lerman LO, Lerman A. Viral endothelial dysfunction: A unifying mechanism for COVID-19. Mayo Clin Proc. 2021;96:3099-108.
- Aydın P, Karabulut Uzunçakmak S ,Tör IH , Bilen A , Özden A. Comparison of serum adropin levels in patients with diabetes mellitus, COVID-19, and COVID-19 with diabetes mellitus. Eurasian J Med. 2022;54:197-201.
- Goshua G, Pine AB, Meizlish ML, Chang CH, Zhang H, Bahel P et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020;7:e575-82.
- Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol. 2000;20:2032-7.
- Hannemann J, Balfanz P, Schwedhelm E, Hartmann B, Ule J, Müller-Wieland D et al. Elevated serum SDMA and ADMA at hospital admission predict in-hospital mortality of COVID-19 patients. Sci Rep. 2021;11:9895.
- Emlek N, Yilmaz AS, Ergul E, Gundogdu H, Arpa M, Koc H, et al. The relationship of serum asymmetric dimethylarginine concentrations and lung involvement in patients with COVID-19 infection. Exp Biomed Res. 2021;4:314-21.
- Farhangrazi, Shadi Z, Moghimi SM. Elevated circulating endothelin-1 as a potential biomarker for high-risk COVID-19 severity. Precis Nanomed. 2020;3:622-28.
- Abraham GR, Kuc RE, Althage M, Greasley PJ, Ambery P, Maguire JJ et al. Endothelin-1 is increased in the plasma of patients hospitalized with Covid-19. J Mol Cell Cardiol. 2022;167:92-6.
- Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012:33:829-37.
- Guan SP, Seet RCS, Kennedy BK. Does eNOS derived nitric oxide protect the young from severe COVID-19 complications? Ageing Res Rev. 2020;64:101201.
- Green SJ. Covid-19 accelerates endothelial dysfunction and nitric oxide deficiency. Microbes Infect. 2020;22:149-50.
- Tong M, Jiang Y, Xia D, Xiong Y, Zheng Q, Chen F et al. Elevated expression of serum endothelial cell adhesion molecules in COVID-19 patients. J Infect Dis. 2020;222:894–8.
- Vassiliou AG, Keskinidou C, Jahaj E, Gallos P, Dimopoulou I, Kotanidou A et al. ICU admission levels of endothelial biomarkers as predictors of mortality in critically Ill COVID-19 patients. Cells. 2021;10:186.
- Dellas C, Loskutoff DJ. Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost. 2005;93:631-40.
- Vaughan DE. PAI-1 and atherothrombosis. J Thromb Haemost. 2005;3:1879-83.
- Baluta MM, Vintila MM. PAI-1 inhibition - another therapeutic option for cardiovascular protection. Maedica (Bucur). 2015;10:147-52.
- Ranucci M, Ballotta A, Di Dedda U, Bayshnikova E, Dei Poli M, Resta M et al. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost. 2020;18:1747-51.
- Masi P, Hekimian G, Lejeune M, Chommeloux J, Desnos C, De Chambrun MP et al. Systemic inflammatory response syndrome is a major contributor to COVID-19-associated coagulopathy: Insights from a prospective, single-center cohort study. Circulation. 2020;142:611-4.
- Zuo Y, Warnock M, Harbaugh A, Yalavarthi S, Gockman K, Zuo M et al. Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients. Sci Rep. 2021;11:1580.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Research |
| Authors | |
| Project Number | 2021-04-01-MAP13 |
| Early Pub Date | July 10, 2023 |
| Publication Date | July 2, 2023 |
| Acceptance Date | June 1, 2023 |
| Published in Issue | Year 2023 Volume: 48 Issue: 2 |
