Soluble Receptor for Advanced Glycation End Products and Its Forms in COVID-19 Patients with and without Diabetes Mellitus: A Pilot Study on Their Role as Disease Biomarkers
Abstract
:1. Introduction
2. Experimental Section
2.1. Study Design and Participants
2.2. Quantification of sRAGE, esRAGE and cRAGE
2.3. Quantification of Glycated Albumin
2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Schmidt, A.M. Soluble RAGEs—Prospects for treating & tracking metabolic and inflammatory disease. Vasc. Pharm. 2015, 72, 1–8. [Google Scholar] [CrossRef] [Green Version]
- Egana-Gorrono, L.; Lopez-Diez, R.; Yepuri, G.; Ramirez, L.S.; Reverdatto, S.; Gugger, P.F.; Shekhtman, A.; Ramasamy, R.; Schmidt, A.M. Receptor for Advanced Glycation End Products (RAGE) and Mechanisms and Therapeutic Opportunities in Diabetes and Cardiovascular Disease: Insights From Human Subjects and Animal Models. Front. Cardiovasc. Med. 2020, 7, 37. [Google Scholar] [CrossRef] [PubMed]
- Oczypok, E.A.; Perkins, T.N.; Oury, T.D. All the “RAGE” in lung disease: The receptor for advanced glycation endproducts (RAGE) is a major mediator of pulmonary inflammatory responses. Paediatr. Respir. Rev. 2017, 23, 40–49. [Google Scholar] [CrossRef] [PubMed]
- Selvin, E.; Halushka, M.K.; Rawlings, A.M.; Hoogeveen, R.C.; Ballantyne, C.M.; Coresh, J.; Astor, B.C. sRAGE and risk of diabetes, cardiovascular disease, and death. Diabetes 2013, 62, 2116–2121. [Google Scholar] [CrossRef] [Green Version]
- Dozio, E.; Vianello, E.; Briganti, S.; Lamont, J.; Tacchini, L.; Schmitz, G.; Corsi Romanelli, M.M. Expression of the Receptor for Advanced Glycation End Products in Epicardial Fat: Link with Tissue Thickness and Local Insulin Resistance in Coronary Artery Disease. J. Diabetes Res. 2016, 2016, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Dozio, E.; Vianello, E.; Sitzia, C.; Ambrogi, F.; Benedini, S.; Gorini, S.; Rampoldi, B.; Rigolini, R.; Tacchini, L.; Romanelli, M.M.C. Circulating Irisin and esRAGE as Early Biomarkers of Decline of Metabolic Health. J. Clin. Med. 2020, 9, 454. [Google Scholar] [CrossRef] [Green Version]
- Boteanu, R.M.; Uyy, E.; Suica, V.I.; Antohe, F. High-mobility group box 1 enhances the inflammatory process in diabetic lung. Arch. Biochem. Biophys. 2015, 583, 55–64. [Google Scholar] [CrossRef]
- Rojas, A.; Gonzalez, I.; Morales, M.A. SARS-CoV-2-mediated inflammatory response in lungs: Should we look at RAGE? Inflamm. Res. 2020, 69, 641–643. [Google Scholar] [CrossRef]
- Pickering, R.J.; Tikellis, C.; Rosado, C.J.; Tsorotes, D.; Dimitropoulos, A.; Smith, M.; Huet, O.; Seeber, R.M.; Abhayawardana, R.; Johnstone, E.K.; et al. Transactivation of RAGE mediates angiotensin-induced inflammation and atherogenesis. J. Clin. Investig. 2019, 129, 406–421. [Google Scholar] [CrossRef]
- Zhang, S.; Liu, Y.; Wang, X.; Yang, L.; Li, H.; Wang, Y.; Liu, M.; Zhao, X.; Xie, Y.; Yang, Y.; et al. SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. J. Hematol. Oncol. 2020, 13, 120. [Google Scholar] [CrossRef]
- Zhao, P.; Praissman, J.L.; Grant, O.C.; Cai, Y.; Xiao, T.; Rosenbalm, K.E.; Aoki, K.; Kellman, B.P.; Bridger, R.; Barouch, D.H.; et al. Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor. Cell Host Microbe 2020. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Chen, S.; Bihl, J. Exosome-Mediated Transfer of ACE2 (Angiotensin-Converting Enzyme 2) from Endothelial Progenitor Cells Promotes Survival and Function of Endothelial Cell. Oxid. Med. Cell. Longev. 2020, 2020, 4213541. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Krishnamachary, B.; Cook, C.; Spikes, L.; Chalise, P.; Dhillon, N.K. The Potential Role of Extracellular Vesicles in COVID-19 Associated Endothelial injury and Pro-inflammation. medRxiv 2020. [Google Scholar] [CrossRef]
- Arunachalam, P.S.; Wimmers, F.; Mok, C.K.P.; Perera, R.; Scott, M.; Hagan, T.; Sigal, N.; Feng, Y.; Bristow, L.; Tak-Yin Tsang, O.; et al. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. Science 2020, 369, 1210–1220. [Google Scholar] [CrossRef] [PubMed]
- Malavazos, A.E.; Corsi, M.M.; Ermetici, F.; Coman, C.; Sardanelli, F.; Rossi, A.; Morricone, L.; Ambrosi, B. Proinflammatory cytokines and cardiac abnormalities in uncomplicated obesity: Relationship with abdominal fat deposition. Nutr. Metab. Cardiovasc. Dis. 2007, 17, 294–302. [Google Scholar] [CrossRef] [PubMed]
- Benedini, S.; Dozio, E.; Invernizzi, P.L.; Vianello, E.; Banfi, G.; Terruzzi, I.; Luzi, L.; Corsi Romanelli, M.M. Irisin: A Potential Link between Physical Exercise and Metabolism-An Observational Study in Differently Trained Subjects, from Elite Athletes to Sedentary People. J. Diabetes Res. 2017, 2017, 1039161. [Google Scholar] [CrossRef] [PubMed]
- Kouzuma, T.; Usami, T.; Yamakoshi, M.; Takahashi, M.; Imamura, S. An enzymatic method for the measurement of glycated albumin in biological samples. Clin. Chim. Acta 2002, 324, 61–71. [Google Scholar] [CrossRef]
- Kouzuma, T.; Uemastu, Y.; Usami, T.; Imamura, S. Study of glycated amino acid elimination reaction for an improved enzymatic glycated albumin measurement method. Clin. Chim. Acta 2004, 346, 135–143. [Google Scholar] [CrossRef]
- Kohzuma, T.; Yamamoto, T.; Uematsu, Y.; Shihabi, Z.K.; Freedman, B.I. Basic performance of an enzymatic method for glycated albumin and reference range determination. J. Diabetes Sci. Technol. 2011, 5, 1455–1462. [Google Scholar] [CrossRef] [Green Version]
- Roncon, L.; Zuin, M.; Rigatelli, G.; Zuliani, G. Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome. J. Clin. Virol. 2020, 127, 104354. [Google Scholar] [CrossRef]
- De Francesco, E.M.; Vella, V.; Belfiore, A. COVID-19 and Diabetes: The Importance of Controlling RAGE. Front. Endocrinol. 2020, 11, 526. [Google Scholar] [CrossRef] [PubMed]
- 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, 1417–1418. [Google Scholar] [CrossRef]
- Schlueter, C.; Hauke, S.; Flohr, A.M.; Rogalla, P.; Bullerdiek, J. Tissue-specific expression patterns of the RAGE receptor and its soluble forms--a result of regulated alternative splicing? Biochim. Biophys. Acta 2003, 1630, 1–6. [Google Scholar] [CrossRef] [PubMed]
- Raucci, A.; Cugusi, S.; Antonelli, A.; Barabino, S.M.; Monti, L.; Bierhaus, A.; Reiss, K.; Saftig, P.; Bianchi, M.E. A soluble form of the receptor for advanced glycation endproducts (RAGE) is produced by proteolytic cleavage of the membrane-bound form by the sheddase a disintegrin and metalloprotease 10 (ADAM10). FASEB J. 2008, 22, 3716–3727. [Google Scholar] [CrossRef] [PubMed]
- Zhang, L.; Bukulin, M.; Kojro, E.; Roth, A.; Metz, V.V.; Fahrenholz, F.; Nawroth, P.P.; Bierhaus, A.; Postina, R. Receptor for advanced glycation end products is subjected to protein ectodomain shedding by metalloproteinases. J. Biol. Chem. 2008, 283, 35507–35516. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Selejan, S.R.; Hewera, L.; Hohl, M.; Kazakov, A.; Ewen, S.; Kindermann, I.; Bohm, M.; Link, A. Suppressed MMP-9 Activity in Myocardial Infarction-Related Cardiogenic Shock Implies Diminished Rage Degradation. Shock 2017, 48, 18–28. [Google Scholar] [CrossRef]
- Lee, A.C.; Lam, J.K.; Shiu, S.W.; Wong, Y.; Betteridge, D.J.; Tan, K.C. Serum Level of Soluble Receptor for Advanced Glycation End Products Is Associated with A Disintegrin And Metalloproteinase 10 in Type 1 Diabetes. PLoS ONE 2015, 10, e0137330. [Google Scholar] [CrossRef] [Green Version]
- Stilhano, R.S.; Costa, A.J.; Nishino, M.S.; Shams, S.; Bartolomeo, C.S.; Breithaupt-Faloppa, A.C.; Silva, E.A.; Ramirez, A.L.; Prado, C.M.; Ureshino, R.P. SARS-CoV-2 and the possible connection to ERs, ACE2, and RAGE: Focus on susceptibility factors. FASEB J. 2020. [Google Scholar] [CrossRef]
- Vazzana, N.; Santilli, F.; Cuccurullo, C.; Davi, G. Soluble forms of RAGE in internal medicine. Intern. Emerg. Med. 2009, 4, 389–401. [Google Scholar] [CrossRef]
- Hudson, B.I.; Moon, Y.P.; Kalea, A.Z.; Khatri, M.; Marquez, C.; Schmidt, A.M.; Paik, M.C.; Yoshita, M.; Sacco, R.L.; DeCarli, C.; et al. Association of serum soluble receptor for advanced glycation end-products with subclinical cerebrovascular disease: The Northern Manhattan Study (NOMAS). Atherosclerosis 2011, 216, 192–198. [Google Scholar] [CrossRef] [Green Version]
- Hudson, B.I.; Carter, A.M.; Harja, E.; Kalea, A.Z.; Arriero, M.; Yang, H.; Grant, P.J.; Schmidt, A.M. Identification, classification, and expression of RAGE gene splice variants. FASEB J. 2008, 22, 1572–1580. [Google Scholar] [CrossRef]
DM+ | DM− | CTR | |
---|---|---|---|
N | 11 | 22 | 99 |
Age, years | 72.6 (15.8) *,° | 55.6 (22.5) ° | 43.5 (11.5) |
Males (n, %) | 8 (72.7) | 13 (59) | 53 (53.5) |
COVID-19 Severity | |||
Mild (n, %) | 4 (36.4) | 11 (50.0) | - |
Moderate (n, %) | 6 (54.5) | 7 (31.8) | - |
Severe (n, %) | 1 (9.1) | 4 (18.2) | - |
Other comorbidities | |||
Hypertension (n, %) | 5 (45.5) | 6 (27.3) | - |
History of cardiovascular disease (n, %) | 4 (36.4) | 2 (9.1) | - |
Chronic renal disease (n, %) | 1 (9.1) | 1 (4.5) | - |
COPD (n, %) | 1 (9.1) | 1 (4.5) | - |
Smoking (n, %) | 1 (9.1) | - | - |
Biochemical data | |||
CRP (mg/dL) | 5.5 (5.6) | 5.8 (6.6) | - |
eGFR (mL/min/1.73 m2) | 58.4 (20.6) *,° | 73.6 (23.4) | 84.0 (8.9) |
White blood cell count (×1000/µL) | 8.90 | 7.20 | - |
Drugs | |||
Antidiabetic drugs (n, %) | 11 (100) +,° | - | - |
Aspirin (n, %) | 3 (27.3) | 2 (9.1) | - |
ACEI/ARB (n, %) | 2 (18.2) | 4 (18.2) | - |
β-Blockers (n, %) | 3 (27.3) | 4 (18.2) | - |
Calcium channel blokers (n, %) | 1 (9.1) | 3 (13.6) | - |
Statins (n, %) | 3 (27.3) | 1 (4.5) | - |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Dozio, E.; Sitzia, C.; Pistelli, L.; Cardani, R.; Rigolini, R.; Ranucci, M.; Corsi Romanelli, M.M. Soluble Receptor for Advanced Glycation End Products and Its Forms in COVID-19 Patients with and without Diabetes Mellitus: A Pilot Study on Their Role as Disease Biomarkers. J. Clin. Med. 2020, 9, 3785. https://doi.org/10.3390/jcm9113785
Dozio E, Sitzia C, Pistelli L, Cardani R, Rigolini R, Ranucci M, Corsi Romanelli MM. Soluble Receptor for Advanced Glycation End Products and Its Forms in COVID-19 Patients with and without Diabetes Mellitus: A Pilot Study on Their Role as Disease Biomarkers. Journal of Clinical Medicine. 2020; 9(11):3785. https://doi.org/10.3390/jcm9113785
Chicago/Turabian StyleDozio, Elena, Clementina Sitzia, Lara Pistelli, Rosanna Cardani, Roberta Rigolini, Marco Ranucci, and Massimiliano M. Corsi Romanelli. 2020. "Soluble Receptor for Advanced Glycation End Products and Its Forms in COVID-19 Patients with and without Diabetes Mellitus: A Pilot Study on Their Role as Disease Biomarkers" Journal of Clinical Medicine 9, no. 11: 3785. https://doi.org/10.3390/jcm9113785