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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Meta-Analysis

The Role of Endothelial Related Circulating Biomarkers in COVID-19. A Systematic Review and Meta-analysis

Author(s): Stamatios Lampsas, Paraskevas Tsaplaris, Panteleimon Pantelidis, Evangelos Oikonomou*, Georgios Marinos, Georgios Charalambous, Nektarios Souvaliotis, Vasiliki-Chara Mystakidi, Athina Goliopoulou, Efstratios Katsianos, Gerasimos Siasos, Michael-Andrew Vavuranakis, Costas Tsioufis, Manolis Vavuranakis and Dimitrios Tousoulis

Volume 29, Issue 21, 2022

Published on: 27 December, 2021

Page: [3790 - 3805] Pages: 16

DOI: 10.2174/0929867328666211026124033

Price: $65

Abstract

Background: Several studies have revealed the link between Coronavirus Disease 2019 (COVID-19) and endothelial dysfunction. To better understand the global pattern of this relationship, we conducted a meta-analysis on endothelial biomarkers related to COVID-19 severity.

Methods: We systematically searched the literature up to March 10, 2021, for studies investigating the association between COVID-19 severity and the following endothelial biomarkers: Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), E-selectin, P-selectin, Von Willebrand Factor Antigen (VWFAg), soluble Thrombomodulin (sTM), Mid-regional pro-adrenomedullin (MR-proADM), and Angiopoietin-2 (Ang-2). Pooled estimates and mean differences (PMD) for each biomarker were reported.

Results: A total of 27 studies (n=2213 patients) were included. Critically ill patients presented with higher levels of MR-proADM (PMD: 0.71 nmol/L, 95% CI: 0.22 to 1.20 nmol/L, p=0.02), E-selectin (PMD: 13,32 pg/ml, 95% CI: 4,89 to 21,75 pg/ml, p=0.008), VCAM-1 (PMD: 479 ng/ml, 95% CI: 64 to 896 ng/ml, p=0.03), VWF-Ag (PMD: 110.5 IU/dl, 95% CI: 44.8 to 176.1 IU/dl, p=0.04) and Ang-2 (PMD: 2388 pg/ml, 95% CI: 1121 to 3655 pg/ml, p=0.003), as compared to non-critically ill ones. ICAM-1, P-selectin and thrombomodulin did not differ between the two groups (p>0.05).

Conclusion: Endothelial biomarkers display significant heterogeneity in COVID-19 patients, with higher MR-proADM, E-selectin, VCAM-1, VWF-Ag, and Ang-2 levels being associated with increased severity. These findings strengthen the evidence on the key role of endothelial dysfunction in disease progress.

Keywords: COVID-19, SARS-CoV-2, endothelial dysfunction, biomarkers, adhesion molecules, disease severity.

[1]
WHO. WHO Director-General’s opening remarks at the media briefing on COVID-19. 2020. Available from: https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 (Accessed: Apr 24, 2021).
[2]
WHO; WHO Coronavirus (COVID-19) Dashboard. Available from: https://covid19.who.int (Accessed: Apr 24, 2021).
[3]
Zaim, S.; Chong, J.H.; Sankaranarayanan, V.; Harky, A. COVID-19 and multiorgan response. Curr. Probl. Cardiol., 2020, 45(8), 100618.
[http://dx.doi.org/10.1016/j.cpcardiol.2020.100618] [PMID: 32439197]
[4]
Mokhtari, T.; Hassani, F.; Ghaffari, N.; Ebrahimi, B.; Yarahmadi, A.; Hassanzadeh, G. COVID-19 and multiorgan failure: A narrative review on potential mechanisms. J. Mol. Histol., 2020, 51(6), 613-628.
[http://dx.doi.org/10.1007/s10735-020-09915-3] [PMID: 33011887]
[5]
Darif, D.; Hammi, I.; Kihel, A.; El Idrissi Saik, I.; Guessous, F.; Akarid, K. The pro-inflammatory cytokines in COVID-19 pathogenesis: what goes wrong? Microb. Pathog., 2021, 153, 104799.
[http://dx.doi.org/10.1016/j.micpath.2021.104799] [PMID: 33609650]
[6]
Varga, Z.; Flammer, A.J.; Steiger, P.; Haberecker, M.; Andermatt, R.; Zinkernagel, A.S.; Mehra, M.R.; Schuepbach, R.A.; Ruschitzka, F.; Moch, H. Endothelial cell infection and endotheliitis in COVID-19. Lancet, 2020, 395(10234), 1417-1418.
[http://dx.doi.org/10.1016/S0140-6736(20)30937-5] [PMID: 32325026]
[7]
de Guadiana-Romualdo, L.G.; Nieves, M.D.C.; Mulero, M.D.R.; Alises, I.C.; Olivo, M.H.; Fernández, W.T.; Morales, M.G.; Jiménez, C.B.; Albaladejo-Otón, M.D.; Ovalle, H.F.; Hernández, A.C.; Manrique, E.A.; Consuegra-Sánchez, L.; Martín, L.N.; Zamora, P.C.; Andaluz-Ojeda, D. MR-proADM as marker of endotheliitis predicts COVID-19 severity. Eur. J. Clin. Invest., 2021, 51(5), e13511.
[http://dx.doi.org/10.1111/eci.13511] [PMID: 33569769]
[8]
Leite, A.R.; Borges-Canha, M.; Cardoso, R.; Neves, J.S.; Castro-Ferreira, R.; Leite-Moreira, A. Novel biomarkers for evaluation of endothelial dysfunction. Angiology, 2020, 71(5), 397-410.
[http://dx.doi.org/10.1177/0003319720903586] [PMID: 32077315]
[9]
Tong, M.; Jiang, Y.; Xia, D.; Xiong, Y.; Zheng, Q.; Chen, F.; Zou, L.; Xiao, W.; Zhu, Y. Elevated expression of serum endothelial cell adhesion molecules in COVID-19 patients. J. Infect. Dis., 2020, 222(6), 894-898.
[http://dx.doi.org/10.1093/infdis/jiaa349] [PMID: 32582936]
[10]
Agrati, C.; Bordoni, V.; Sacchi, A.; Petrosillo, N.; Nicastri, E.; Del Nonno, F.; D’Offizi, G.; Palmieri, F.; Marchioni, L.; Capobianchi, M.R.; Antinori, A.; Ippolito, G.; Bibas, M. Elevated P-selectin in severe Covid-19: considerations for therapeutic options. Mediterr. J. Hematol. Infect. Dis., 2021, 13(1), e2021016.
[http://dx.doi.org/10.4084/mjhid.2021.016] [PMID: 33747397]
[11]
Philippe, A.; Chocron, R.; Gendron, N.; Bory, O.; Beauvais, A.; Peron, N.; Khider, L.; Guerin, C.L.; Goudot, G.; Levasseur, F.; Peronino, C.; Duchemin, J.; Brichet, J.; Sourdeau, E.; Desvard, F.; Bertil, S.; Pene, F.; Cheurfa, C.; Szwebel, T.A.; Planquette, B.; Rivet, N.; Jourdi, G.; Hauw-Berlemont, C.; Hermann, B.; Gaussem, P.; Mirault, T.; Terrier, B.; Sanchez, O.; Diehl, J.L.; Fontenay, M.; Smadja, D.M. Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality. Angiogenesis, 2021, 24(3), 505-517.
[http://dx.doi.org/10.1007/s10456-020-09762-6] [PMID: 33449299]
[12]
Cugno, M.; Meroni, P.L.; Gualtierotti, R.; Griffini, S.; Grovetti, E.; Torri, A.; Lonati, P.; Grossi, C.; Borghi, M.O.; Novembrino, C.; Boscolo, M.; Uceda Renteria, S.C.; Valenti, L.; Lamorte, G.; Manunta, M.; Prati, D.; Pesenti, A.; Blasi, F.; Costantino, G.; Gori, A.; Bandera, A.; Tedesco, F.; Peyvandi, F. Complement activation and endothelial perturbation parallel COVID-19 severity and activity. J. Autoimmun., 2021, 116, 102560.
[http://dx.doi.org/10.1016/j.jaut.2020.102560] [PMID: 33139116]
[13]
Goshua, G.; Pine, A.B.; Meizlish, M.L.; Chang, C-H.; Zhang, H.; Bahel, P.; Baluha, A.; Bar, N.; Bona, R.D.; Burns, A.J.; Dela Cruz, C.S.; Dumont, A.; Halene, S.; Hwa, J.; Koff, J.; Menninger, H.; Neparidze, N.; Price, C.; Siner, J.M.; Tormey, C.; Rinder, H.M.; Chun, H.J.; Lee, A.I. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol., 2020, 7(8), e575-e582.
[http://dx.doi.org/10.1016/S2352-3026(20)30216-7] [PMID: 32619411]
[14]
Bouck, E.G.; Denorme, F.; Holle, L.A.; Middelton, E.A.; Blair, A.M.; de Laat, B.; Schiffman, J.D.; Yost, C.C.; Rondina, M.T.; Wolberg, A.S.; Campbell, R.A. COVID-19 and sepsis are associated with different abnormalities in plasma procoagulant and fibrinolytic activity. Arterioscler. Thromb. Vasc. Biol., 2021, 41(1), 401-414.
[http://dx.doi.org/10.1161/ATVBAHA.120.315338] [PMID: 33196292]
[15]
Sozio, E.; Tascini, C.; Fabris, M.; D’Aurizio, F.; De Carlo, C.; Graziano, E.; Bassi, F.; Sbrana, F.; Ripoli, A.; Pagotto, A.; Giacinta, A.; Gerussi, V.; Visentini, D.; De Stefanis, P.; Merelli, M.; Saeed, K.; Curcio, F. MR-proADM as prognostic factor of outcome in COVID-19 patients. Sci. Rep., 2021, 11(1), 5121.
[http://dx.doi.org/10.1038/s41598-021-84478-1] [PMID: 33664308]
[16]
Gregoriano, C.; Koch, D.; Kutz, A.; Haubitz, S.; Conen, A.; Bernasconi, L.; Hammerer-Lercher, A.; Saeed, K.; Mueller, B.; Schuetz, P. The vasoactive peptide MR-pro-adrenomedullin in COVID-19 patients: An observational study. Clin. Chem. Lab. Med., 2021, 59(5), 995-1004.
[http://dx.doi.org/10.1515/cclm-2020-1295] [PMID: 33554516]
[17]
Pine, A.B.; Meizlish, M.L.; Goshua, G.; Chang, C-H.; Zhang, H.; Bishai, J.; Bahel, P.; Patel, A.; Gbyli, R.; Kwan, J.M.; Won, C.H.; Price, C.; Dela Cruz, C.S.; Halene, S.; van Dijk, D.; Hwa, J.; Lee, A.I.; Chun, H.J. Circulating markers of angiogenesis and endotheliopathy in COVID-19. Pulm. Circ., 2020, 10(4), 2045894020966547.
[http://dx.doi.org/10.1177/2045894020966547] [PMID: 33282193]
[18]
Vassiliou, A.G.; Keskinidou, C.; Jahaj, E.; Gallos, P.; Dimopoulou, I.; Kotanidou, A.; Orfanos, S.E. ICU admission levels of endothelial biomarkers as predictors of mortality in critically ill COVID-19 patients. Cells, 2021, 10(1), 186.
[http://dx.doi.org/10.3390/cells10010186] [PMID: 33477776]
[19]
Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G.; Altman, D.; Antes, G.; Atkins, D.; Barbour, V.; Barrowman, N.; Berlin, J.A. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med., 2009, 6(7), e1000097.
[http://dx.doi.org/10.1371/journal.pmed.1000097] [PMID: 19621072]
[20]
Wells, G.A.; Shea, B.; O’Connell, D.; Peterson, J.; Welch, V.; Losos, M.; Tugwell, P. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses; Oxford, 2000.
[21]
Wan, X.; Wang, W.; Liu, J.; Tong, T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med. Res. Methodol., 2014, 14, 135.
[http://dx.doi.org/10.1186/1471-2288-14-135] [PMID: 25524443]
[22]
Higgins, J.P.T.; Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med., 2002, 21(11), 1539-1558.
[http://dx.doi.org/10.1002/sim.1186] [PMID: 12111919]
[23]
Egger, M.; Davey Smith, G.; Schneider, M.; Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997, 315(7109), 629-634.
[http://dx.doi.org/10.1136/bmj.315.7109.629] [PMID: 9310563]
[24]
Abers, M.S.; Delmonte, O.M.; Ricotta, E.E.; Fintzi, J.; Fink, D.L.; de Jesus, A.A.A.; Zarember, K.A.; Alehashemi, S.; Oikonomou, V.; Desai, J.V.; Canna, S.W.; Shakoory, B.; Dobbs, K.; Imberti, L.; Sottini, A.; Quiros-Roldan, E.; Castelli, F.; Rossi, C.; Brugnoni, D.; Biondi, A.; Bettini, L.R.; D’Angio’, M.; Bonfanti, P.; Castagnoli, R.; Montagna, D.; Licari, A.; Marseglia, G.L.; Gliniewicz, E.F.; Shaw, E.; Kahle, D.E.; Rastegar, A.T.; Stack, M.; Myint-Hpu, K.; Levinson, S.L.; DiNubile, M.J.; Chertow, D.W.; Burbelo, P.D.; Cohen, J.I.; Calvo, K.R.; Tsang, J.S.; Su, H.C.; Gallin, J.I.; Kuhns, D.B.; Goldbach-Mansky, R.; Lionakis, M.S.; Notarangelo, L.D. An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI Insight, 2021, 6(1), 144455.
[http://dx.doi.org/10.1172/jci.insight.144455] [PMID: 33232303]
[25]
Bauer, W.; Ulke, J.; Galtung, N.; Strasser-Marsik, L.C.; Neuwinger, N.; Tauber, R.; Somasundaram, R.; Kappert, K. Role of cell adhesion molecules for prognosis of disease development of patients with and without COVID-19 in the emergency department. J. Infect. Dis., 2021, 223(8), 1497-1499.
[http://dx.doi.org/10.1093/infdis/jiab042] [PMID: 33502532]
[26]
Bazzan, M.; Montaruli, B.; Sciascia, S.; Cosseddu, D.; Norbiato, C.; Roccatello, D. Low ADAMTS 13 plasma levels are predictors of mortality in COVID-19 patients. Intern. Emerg. Med., 2020, 15(5), 861-863.
[http://dx.doi.org/10.1007/s11739-020-02394-0] [PMID: 32557383]
[27]
Bermejo-Martin, J.F.; González-Rivera, M.; Almansa, R.; Micheloud, D.; Tedim, A.P.; Domínguez-Gil, M.; Resino, S.; Martín-Fernández, M.; Ryan Murua, P.; Pérez-García, F.; Tamayo, L.; Lopez-Izquierdo, R.; Bustamante, E.; Aldecoa, C.; Gómez, J.M.; Rico-Feijoo, J.; Orduña, A.; Méndez, R.; Fernández Natal, I.; Megías, G.; González-Estecha, M.; Carriedo, D.; Doncel, C.; Jorge, N.; Ortega, A.; de la Fuente, A.; Del Campo, F.; Fernández-Ratero, J.A.; Trapiello, W.; González-Jiménez, P.; Ruiz, G.; Kelvin, A.A.; Ostadgavahi, A.T.; Oneizat, R.; Ruiz, L.M.; Miguéns, I.; Gargallo, E.; Muñoz, I.; Pelegrin, S.; Martín, S.; García Olivares, P.; Cedeño, J.A.; Ruiz Albi, T.; Puertas, C.; Berezo, J.Á.; Renedo, G.; Herrán, R.; Bustamante-Munguira, J.; Enríquez, P.; Cicuendez, R.; Blanco, J.; Abadia, J.; Gómez Barquero, J.; Mamolar, N.; Blanca-López, N.; Valdivia, L.J.; Fernández Caso, B.; Mantecón, M.Á.; Motos, A.; Fernandez-Barat, L.; Ferrer, R.; Barbé, F.; Torres, A.; Menéndez, R.; Eiros, J.M.; Kelvin, D.J. Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19. Crit. Care, 2020, 24(1), 691.
[http://dx.doi.org/10.1186/s13054-020-03398-0] [PMID: 33317616]
[28]
Campo, G.; Contoli, M.; Fogagnolo, A.; Vieceli Dalla Sega, F.; Zucchetti, O.; Ronzoni, L.; Verri, M.; Fortini, F.; Pavasini, R.; Morandi, L. Over time relationship between platelet reactivity, myocardial injury and mortality in patients with SARS-CoV-2-associated respiratory failure. Platelets, 2020, 32(4), 1-8.
[http://dx.doi.org/10.1080/09537104.2020.1852543] [PMID: 33270471]
[29]
De Jongh, R.; Ninivaggi, M.; Mesotten, D.; Bai, C.; Marcus, B.; Huskens, D.; Stragier, H.; Miszta, A.; Verbruggen, J.; de Laat-Kremers, R.M.W. Vascular activation is a strong predictor of mortality in coronavirus disease 2019 patients on the ICU. Blood Coagul. Fibrinolysis, 2021, 32(4), 290-293.
[http://dx.doi.org/10.1097/MBC.0000000000001007]
[30]
Dupont, A.; Rauch, A.; Staessens, S.; Moussa, M.; Rosa, M.; Corseaux, D.; Jeanpierre, E.; Goutay, J.; Caplan, M.; Varlet, P.; Lefevre, G.; Lassalle, F.; Bauters, A.; Faure, K.; Lambert, M.; Duhamel, A.; Labreuche, J.; Garrigue, D.; De Meyer, S.F.; Staels, B.; Vincent, F.; Rousse, N.; Kipnis, E.; Lenting, P.; Poissy, J.; Susen, S. Vascular endothelial damage in the pathogenesis of organ injury in severe COVID-19. Arterioscler. Thromb. Vasc. Biol., 2021, 41(5), 1760-1773.
[http://dx.doi.org/10.1161/ATVBAHA.120.315595] [PMID: 33626910]
[31]
Guervilly, C.; Burtey, S.; Sabatier, F.; Cauchois, R.; Lano, G.; Abdili, E.; Daviet, F.; Arnaud, L.; Brunet, P.; Hraiech, S.; Jourde-Chiche, N.; Koubi, M.; Lacroix, R.; Pietri, L.; Berda, Y.; Robert, T.; Degioanni, C.; Velier, M.; Papazian, L.; Kaplanski, G.; Dignat-George, F. Circulating endothelial cells as a marker of endothelial injury in severe COVID -19. J. Infect. Dis., 2020, 222(11), 1789-1793.
[http://dx.doi.org/10.1093/infdis/jiaa528] [PMID: 32812049]
[32]
Henry, B.M.; Vikse, J.; Benoit, S.; Favaloro, E.J.; Lippi, G. Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis. Clin. Chim. Acta, 2020, 507, 167-173.
[http://dx.doi.org/10.1016/j.cca.2020.04.027] [PMID: 32348783]
[33]
Ladikou, E.E.; Sivaloganathan, H.; Milne, K.M.; Arter, W.E.; Ramasamy, R.; Saad, R.; Stoneham, S.M.; Philips, B.; Eziefula, A.C.; Chevassut, T. Von Willebrand Factor (vWF): marker of endothelial damage and thrombotic risk in COVID-19? Clin. Med. (Lond.), 2020, 20(5), e178-e182.
[http://dx.doi.org/10.7861/clinmed.2020-0346] [PMID: 32694169]
[34]
Mancini, I.; Baronciani, L.; Artoni, A.; Colpani, P.; Biganzoli, M.; Cozzi, G.; Novembrino, C.; Boscolo Anzoletti, M.; De Zan, V.; Pagliari, M.T.; Gualtierotti, R.; Aliberti, S.; Panigada, M.; Grasselli, G.; Blasi, F.; Peyvandi, F. The ADAMTS13-von Willebrand factor axis in COVID-19 patients. J. Thromb. Haemost., 2021, 19(2), 513-521.
[http://dx.doi.org/10.1111/jth.15191] [PMID: 33230904]
[35]
Montrucchio, G.; Sales, G.; Rumbolo, F.; Palmesino, F.; Fanelli, V.; Urbino, R.; Filippini, C.; Mengozzi, G.; Brazzi, L. Effectiveness of mid-regional pro-adrenomedullin (MR-proADM) as prognostic marker in COVID-19 critically ill patients: an observational prospective study. PLoS One, 2021, 16(2), e0246771.
[http://dx.doi.org/10.1371/journal.pone.0246771] [PMID: 33556140]
[36]
Rauch, A.; Labreuche, J.; Lassalle, F.; Goutay, J.; Caplan, M.; Charbonnier, L.; Rohn, A.; Jeanpierre, E.; Dupont, A.; Duhamel, A.; Faure, K.; Lambert, M.; Kipnis, E.; Garrigue, D.; Lenting, P.J.; Poissy, J.; Susen, S. Coagulation biomarkers are independent predictors of increased oxygen requirements in COVID-19. J. Thromb. Haemost., 2020, 18(11), 2942-2953.
[http://dx.doi.org/10.1111/jth.15067] [PMID: 32881304]
[37]
Rodríguez Rodríguez, M.; Castro Quismondo, N.; Zafra Torres, D.; Gil Alos, D.; Ayala, R.; Martinez-Lopez, J. Increased von Willebrand factor antigen and low ADAMTS13 activity are related to poor prognosis in covid-19 patients. Int. J. Lab. Hematol., 2021, 43(4), O152-O155.
[http://dx.doi.org/10.1111/ijlh.13476] [PMID: 33502080]
[38]
Rovas, A.; Osiaevi, I.; Buscher, K.; Sackarnd, J.; Tepasse, P-R.; Fobker, M.; Kühn, J.; Braune, S.; Göbel, U.; Thölking, G.; Gröschel, A.; Pavenstädt, H.; Vink, H.; Kümpers, P. Microvascular dysfunction in COVID-19: The MYSTIC study. Angiogenesis, 2021, 24(1), 145-157.
[http://dx.doi.org/10.1007/s10456-020-09753-7] [PMID: 33058027]
[39]
Smadja, D.M.; Guerin, C.L.; Chocron, R.; Yatim, N.; Boussier, J.; Gendron, N.; Khider, L.; Hadjadj, J.; Goudot, G.; Debuc, B.; Juvin, P.; Hauw-Berlemont, C.; Augy, J.L.; Peron, N.; Messas, E.; Planquette, B.; Sanchez, O.; Charbit, B.; Gaussem, P.; Duffy, D.; Terrier, B.; Mirault, T.; Diehl, J.L. Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients. Angiogenesis, 2020, 23(4), 611-620.
[http://dx.doi.org/10.1007/s10456-020-09730-0] [PMID: 32458111]
[40]
Spadaro, S.; Fogagnolo, A.; Campo, G.; Zucchetti, O.; Verri, M.; Ottaviani, I.; Tunstall, T.; Grasso, S.; Scaramuzzo, V.; Murgolo, F.; Marangoni, E.; Vieceli Dalla Sega, F.; Fortini, F.; Pavasini, R.; Rizzo, P.; Ferrari, R.; Papi, A.; Volta, C.A.; Contoli, M. Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients. Crit. Care, 2021, 25(1), 74.
[http://dx.doi.org/10.1186/s13054-021-03499-4] [PMID: 33608030]
[41]
Villa, E.; Critelli, R.; Lasagni, S.; Melegari, A.; Curatolo, A.; Celsa, C.; Romagnoli, D.; Melegari, G.; Pivetti, A.; Di Marco, L.; Casari, F.; Arioli, D.; Turrini, F.; Zuccaro, V.; Cassaniti, I.; Riefolo, M.; de Santis, E.; Bernabucci, V.; Bianchini, M.; Lei, B.; De Maria, N.; Carulli, L.; Schepis, F.; Gozzi, C.; Malaguti, S.; Del Buono, M.; Brugioni, L.; Torricelli, P.; Trenti, T.; Pinelli, G.; Bertellini, E.; Bruno, R.; Cammà, C.; d’Errico, A. Dynamic angiopoietin-2 assessment predicts survival and chronic course in hospitalized patients with COVID-19. Blood Adv., 2021, 5(3), 662-673.
[http://dx.doi.org/10.1182/bloodadvances.2020003736] [PMID: 33560382]
[42]
Sandoo, A.; van Zanten, J.J.C.S.V.; Metsios, G.S.; Carroll, D.; Kitas, G.D. The endothelium and its role in regulating vascular tone. Open Cardiovasc. Med. J., 2010, 4, 302-312.
[http://dx.doi.org/10.2174/1874192401004010302] [PMID: 21339899]
[43]
Vischer, U.M. von Willebrand factor, endothelial dysfunction, and cardiovascular disease. J. Thromb. Haemost., 2006, 4(6), 1186-1193.
[http://dx.doi.org/10.1111/j.1538-7836.2006.01949.x] [PMID: 16706957]
[44]
Albini, A.; Di Guardo, G.; Noonan, D.M.; Lombardo, M. The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies. Intern. Emerg. Med., 2020, 15(5), 759-766.
[http://dx.doi.org/10.1007/s11739-020-02364-6] [PMID: 32430651]
[45]
Galley, H.F.; Webster, N.R. Physiology of the endothelium. Br. J. Anaesth., 2004, 93(1), 105-113.
[http://dx.doi.org/10.1093/bja/aeh163] [PMID: 15121728]
[46]
Lip, G.Y.H.; Blann, A. von Willebrand factor: A marker of endothelial dysfunction in vascular disorders? Cardiovasc. Res., 1997, 34(2), 255-265.
[http://dx.doi.org/10.1016/S0008-6363(97)00039-4] [PMID: 9205537]
[47]
Dhanesha, N.; Prakash, P.; Doddapattar, P.; Khanna, I.; Pollpeter, M.J.; Nayak, M.K.; Staber, J.M.; Chauhan, A.K. Endothelial cell-derived von Willebrand factor is the major determinant that mediates von Willebrand factor-dependent acute ischemic stroke by promoting postischemic thrombo-inflammation. Arterioscler. Thromb. Vasc. Biol., 2016, 36(9), 1829-1837.
[http://dx.doi.org/10.1161/ATVBAHA.116.307660] [PMID: 27444201]
[48]
Panigada, M.; Bottino, N.; Tagliabue, P.; Grasselli, G.; Novembrino, C.; Chantarangkul, V.; Pesenti, A.; Peyvandi, F.; Tripodi, A. Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis. J. Thromb. Haemost., 2020, 18(7), 1738-1742.
[http://dx.doi.org/10.1111/jth.14850] [PMID: 32302438]
[49]
Taus, F.; Salvagno, G.; Canè, S.; Fava, C.; Mazzaferri, F.; Carrara, E.; Petrova, V.; Barouni, R.M.; Dima, F.; Dalbeni, A.; Romano, S.; Poli, G.; Benati, M.; De Nitto, S.; Mansueto, G.; Iezzi, M.; Tacconelli, E.; Lippi, G.; Bronte, V.; Minuz, P. Platelets promote thromboinflammation in SARS-CoV-2 pneumonia. Arterioscler. Thromb. Vasc. Biol., 2020, 40(12), 2975-2989.
[http://dx.doi.org/10.1161/ATVBAHA.120.315175] [PMID: 33052054]
[50]
Manne, B.K.; Denorme, F.; Middleton, E.A.; Portier, I.; Rowley, J.W.; Stubben, C.; Petrey, A.C.; Tolley, N.D.; Guo, L.; Cody, M.; Weyrich, A.S.; Yost, C.C.; Rondina, M.T.; Campbell, R.A. Platelet gene expression and function in patients with COVID-19. Blood, 2020, 136(11), 1317-1329.
[http://dx.doi.org/10.1182/blood.2020007214] [PMID: 32573711]
[51]
Hottz, E.D.; Azevedo-Quintanilha, I.G.; Palhinha, L.; Teixeira, L.; Barreto, E.A.; Pão, C.R.R.; Righy, C.; Franco, S.; Souza, T.M.L.; Kurtz, P.; Bozza, F.A.; Bozza, P.T. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. Blood, 2020, 136(11), 1330-1341.
[http://dx.doi.org/10.1182/blood.2020007252] [PMID: 32678428]
[52]
Zaid, Y.; Puhm, F.; Allaeys, I.; Naya, A.; Oudghiri, M.; Khalki, L.; Limami, Y.; Zaid, N.; Sadki, K.; Ben El Haj, R.; Mahir, W.; Belayachi, L.; Belefquih, B.; Benouda, A.; Cheikh, A.; Langlois, M.A.; Cherrah, Y.; Flamand, L.; Guessous, F.; Boilard, E. Platelets can associate with SARS-Cov-2 RNA and are hyperactivated in COVID-19. Circ. Res., 2020, 127(11), 1404-1418.
[http://dx.doi.org/10.1161/CIRCRESAHA.120.317703] [PMID: 32938299]
[53]
Helms, J.; Tacquard, C.; Severac, F.; Leonard-Lorant, I.; Ohana, M.; Delabranche, X.; Merdji, H.; Clere-Jehl, R.; Schenck, M.; Fagot Gandet, F.; Fafi-Kremer, S.; Castelain, V.; Schneider, F.; Grunebaum, L.; Anglés-Cano, E.; Sattler, L.; Mertes, P.M.; Meziani, F. High risk of thrombosis in patients with severe SARS-CoV-2 infection: A multicenter prospective cohort study. Intensive Care Med., 2020, 46(6), 1089-1098.
[http://dx.doi.org/10.1007/s00134-020-06062-x] [PMID: 32367170]
[54]
Boffa, M.C.; Karmochkine, M. Thrombomodulin: an overview and potential implications in vascular disorders. Lupus, 1998, 7(Suppl. 2), S120-S125.
[http://dx.doi.org/10.1177/096120339800700227] [PMID: 9814688]
[55]
Martin, F.A.; Murphy, R.P.; Cummins, P.M. Thrombomodulin and the vascular endothelium: insights into functional, regulatory, and therapeutic aspects. Am. J. Physiol. Heart Circ. Physiol., 2013, 304(12), H1585-H1597.
[http://dx.doi.org/10.1152/ajpheart.00096.2013] [PMID: 23604713]
[56]
Miwa, K.; Igawa, A.; Inoue, H. Soluble E-selectin, ICAM-1 and VCAM-1 levels in systemic and coronary circulation in patients with variant angina. Cardiovasc. Res., 1997, 36(1), 37-44.
[http://dx.doi.org/10.1016/S0008-6363(97)00143-0] [PMID: 9415270]
[57]
Muller, W.A. Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol., 2003, 24(6), 327-334.
[http://dx.doi.org/10.1016/S1471-4906(03)00117-0] [PMID: 12810109]
[58]
Chen, N.; Zhou, M.; Dong, X.; Qu, J.; Gong, F.; Han, Y.; Qiu, Y.; Wang, J.; Liu, Y.; Wei, Y.; Xia, J.; Yu, T.; Zhang, X.; Zhang, L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet, 2020, 395(10223), 507-513.
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[59]
Carsana, L.; Sonzogni, A.; Nasr, A.; Rossi, R.S.; Pellegrinelli, A.; Zerbi, P.; Rech, R.; Colombo, R.; Antinori, S.; Corbellino, M.; Galli, M.; Catena, E.; Tosoni, A.; Gianatti, A.; Nebuloni, M. Pulmonary post-mortem findings in a series of COVID-19 cases from Northern Italy: A two-centre descriptive study. Lancet Infect. Dis., 2020, 20(10), 1135-1140.
[http://dx.doi.org/10.1016/S1473-3099(20)30434-5] [PMID: 32526193]
[60]
Davì, G.; Romano, M.; Mezzetti, A.; Procopio, A.; Iacobelli, S.; Antidormi, T.; Bucciarelli, T.; Alessandrini, P.; Cuccurullo, F.; Bittolo Bon, G. Increased levels of soluble P-selectin in hypercholesterolemic patients. Circulation, 1998, 97(10), 953-957.
[http://dx.doi.org/10.1161/01.CIR.97.10.953] [PMID: 9529262]
[61]
Raitakari, O.T.; Celermajer, D.S. Testing for endothelial dysfunction. Ann. Med., 2000, 32(5), 293-304.
[http://dx.doi.org/10.3109/07853890008995931] [PMID: 10949060]
[62]
McEver, R.P. Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc. Res., 2015, 107(3), 331-339.
[http://dx.doi.org/10.1093/cvr/cvv154] [PMID: 25994174]
[63]
de la Sierra, A.; Larrousse, M. Endothelial dysfunction is associated with increased levels of biomarkers in essential hypertension. J. Hum. Hypertens., 2010, 24(6), 373-379.
[http://dx.doi.org/10.1038/jhh.2009.91] [PMID: 19960026]
[64]
Culmer, D.L.; Dunbar, M.L.; Hawley, A.E.; Sood, S.; Sigler, R.E.; Henke, P.K.; Wakefield, T.W.; Magnani, J.L.; Myers, Jr.D.D. E-selectin inhibition with GMI-1271 decreases venous thrombosis without profoundly affecting tail vein bleeding in a mouse model. Thromb. Haemost., 2017, 117(6), 1171-1181.
[http://dx.doi.org/10.1160/TH16-04-0323] [PMID: 28300869]
[65]
Ye, Q.; Wang, B.; Mao, J. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. J. Infect., 2020, 80(6), 607-613.
[http://dx.doi.org/10.1016/j.jinf.2020.03.037] [PMID: 32283152]
[66]
Hu, W.; Zhou, P-H.; Zhang, X-B.; Xu, C-G.; Wang, W. Plasma concentrations of adrenomedullin and natriuretic peptides in patients with essential hypertension. Exp. Ther. Med., 2015, 9(5), 1901-1908.
[http://dx.doi.org/10.3892/etm.2015.2345] [PMID: 26136912]
[67]
Spoto, S.; Agrò, F.E.; Sambuco, F.; Travaglino, F.; Valeriani, E.; Fogolari, M.; Mangiacapra, F.; Costantino, S.; Ciccozzi, M.; Angeletti, S. High value of mid-regional proadrenomedullin in COVID-19: a marker of widespread endothelial damage, disease severity, and mortality. J. Med. Virol., 2021, 93(5), 2820-2827.
[http://dx.doi.org/10.1002/jmv.26676] [PMID: 33200824]
[68]
Pourafkari, L.; Tajlil, A.; Nader, N.D. Biomarkers in diagnosing and treatment of acute heart failure. Biomarkers Med., 2019, 13(14), 1235-1249.
[http://dx.doi.org/10.2217/bmm-2019-0134] [PMID: 31580155]
[69]
Akwii, R.G.; Sajib, M.S.; Zahra, F.T.; Mikelis, C.M. Role of angiopoietin-2 in vascular physiology and pathophysiology. Cells, 2019, 8(5), E471.
[http://dx.doi.org/10.3390/cells8050471] [PMID: 31108880]
[70]
El-Banawy, H.S.; Gaber, E.W.; Maharem, D.A.; Matrawy, K.A. Angiopoietin-2, endothelial dysfunction and renal involvement in patients with systemic lupus erythematosus. J. Nephrol., 2012, 25(4), 541-550.
[http://dx.doi.org/10.5301/jn.5000030] [PMID: 21956768]
[71]
Chang, F-C.; Chiang, W-C.; Tsai, M-H.; Chou, Y-H.; Pan, S-Y.; Chang, Y-T.; Yeh, P-Y.; Chen, Y-T.; Chiang, C-K.; Chen, Y-M.; Chu, T.S.; Wu, K.D.; Lin, S.L. Angiopoietin-2-induced arterial stiffness in CKD. J. Am. Soc. Nephrol., 2014, 25(6), 1198-1209.
[http://dx.doi.org/10.1681/ASN.2013050542] [PMID: 24511140]

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