The pathobiological harmony between the local pulmonary/ bone marrow RAS and its management via tissue-RAS modulating agents in COVID-19

Year 2022, Volume: 5 Issue: 3, 932 - 937, 30.05.2022

Ece Ünal Çetin , Yavuz Beyazıt , Fatma Beyazıt , Alpaslan Tanoğlu , İbrahim Celaleddin Haznedaroğlu

https://doi.org/10.32322/jhsm.1090521

Abstract

Coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented threat to public health and healthcare systems. It presents unusual pathophysiological effects mainly characterized by immune-inflammatory response and prothrombotic state causing acute respiratory distress syndrome and multiple organ failure. SARS-CoV-2 enters target cells after binding to the angiotensin-converting enzyme 2 (ACE2) receptor and therefore has a direct effect on the renin-angiotensin system (RAS). Apart from affecting numerous organs including lungs, heart, gastrointestinal system, spleen, brain and kidneys, the spike protein of SARS-CoV-2 could attack hematopoietic stem cells and hematopoietic progenitor cells in bone marrow (BM) microenvironment together with the precursor and mature blood cells. Within this hematopoietic viral spread context, it is crucial to search the clinicopathological correlations of COVID-19 in order to develop specific potential therapeutics against pleiotropic SARS-CoV-2 actions. Therefore, pharmacological disruption of the pathological cross-talk of local BM RAS and pulmonary RAS via administration of the tissue-RAS modulating agents such as soluble ACE2, angiotensin (1-7), TXA127 and MAS receptor agonists may prevent the clinical progression of the COVID-19 syndrome via reducing the hematopoietic virus propagation and systemic multi-organ spread.

Keywords

COVID-19, SARS-CoV-2, ACE2, renin-angiotensin system, bone marrow

References

• Mutlu P, Mirici A, Gönlügür U, et al. Evaluating the clinical, radiological, microbiological, biochemical parameters and the treatment response in COVID-19 pneumonia. J Health Sci Med 2022; 5: 544-51.
• Haznedaroglu IC. Immunogenomic phases of COVID-19 and appropriate clinical management. Lancet Microbe 2020; 1: e278.
• Güneysu F, Durmuş E. Pre-hospital antithrombotic drug use status of died COVID-19 patients. J Health Sci Med 2021; 4: 564-8.
• Ciftciler R, Ciftciler AE, Haznedaroglu IC. Local bone marrow renin-angiotensin system and COVID-19. Int J Hematol Oncol 2020; 30: 113-20.
• Kucia M, Bujko K, Ciechanowicz A, et al. The ACE2 receptor for COVID-19 entry is expressed on the surface of hematopoietic stem/progenitor cells and endothelial progenitors as well as their precursor cells and becomes activated in Nlrp3 inflammasome-dependent manner by virus spike protein - a potential pathway leading to a "Cytokine Storm".Blood 2020; 136: 8.
• Ropa J, Cooper S, Capitano ML, Broxmeyer HE. SARS-CoV-2 spike protein induces cellular changes in primitive and mature hematopoietic cells. Blood 2020; 136: 25–6.
• Çiftçiler R, Haznedaroğlu İC. COVID-19, renin-angiotensin system, and hematopoiesis. Turk J Haematol 2020; 37: 207-8.
• Turk C, Turk S, Malkan UY, Haznedaroglu IC. Three critical clinicobiological phases of the human SARS-associated coronavirus infections. Eur Rev Med Pharmacol Sci 2020; 24: 8606-20.
• Turk C, Turk S, Temirci ES, Malkan UY, Haznedaroglu İC. In vitro analysis of the renin-angiotensin system and inflammatory gene transcripts in human bronchial epithelial cells after infection with severe acute respiratory syndrome coronavirus. J Renin Angiotensin Aldosterone Syst 2020; 21: 1470320320928872.
• Haznedaroglu IC, Beyazit Y. Local bone marrow renin-angiotensin system in primitive, definitive and neoplastic haematopoiesis. Clin Sci (Lond) 2013; 124: 307-23.
• Haznedaroglu IC, Beyazit Y. Pathobiological aspects of the local bone marrow renin-angiotensin system: a review. J Renin Angiotensin Aldosterone Syst 2010; 11: 205-13.
• Saponaro F, Rutigliano G, Sestito S, et al. ACE2 in the Era of SARS-CoV-2: controversies and novel perspectives. Front Mol Biosci 2020; 7: 588618.
• Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 2005; 11: 875-9.
• Ratajczak MZ, Bujko K, Ciechanowicz A, et al. SARS-CoV-2 entry receptor ACE2 is expressed on very small CD45- precursors of hematopoietic and endothelial cells and in response to virus spike protein activates the Nlrp3 inflammasome. Stem Cell Rev Rep 2021: 17: 266-77.
• Marshall RP. The pulmonary renin-angiotensin system. Curr Pharm Des 2003; 9: 715-22.
• Goyal R, Leitzke A, Goyal D, Gheorghe CP, Longo LD. Antenatal maternal hypoxic stress: adaptations in fetal lung Renin-Angiotensin system. Reprod Sci 2011; 18: 180-9.
• Wang D, Chai XQ, Magnussen CG, et al. Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation. Pulm Pharmacol Ther 2019; 58: 101833.
• Lumbers ER, Delforce SJ, Pringle KG, Smith GR. The lung, the heart, the novel coronavirus, and the renin-angiotensin system; the need for clinical trials. Front Med (Lausanne) 2020; 7: 248.
• Yoshikawa T, Hill TE, Yoshikawa N, et al. Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection. PLoS One 2010; 5: e8729.
• Wu Y. Compensation of ACE2 function for possible clinical management of 2019-nCoV-induced acute lung injury. Virol Sin 2020; 35: 256-58.
• Pucci F, Bogaerts P, Rooman M. Modeling the molecular impact of SARS-CoV-2 infection on the renin-angiotensin system. Viruses 2020; 12: E1367.
• Beyazit Y, Purnak T, Guven GS, Haznedaroglu IC. Local bone marrow Renin-Angiotensin system and atherosclerosis. Cardiol Res Pract 2010; 2011: 714515.
• Ciftciler R, Haznedaroglu IC. Pathobiological interactions of local bone marrow renin-angiotensin system and central nervous system in systemic arterial hypertension. Front Endocrinol (Lausanne) 2020; 11: 425.
• Ihlow J, von-Bruenneck A-C, Michaelis EG, et al. COVID-19: B-cell depletion and sepsis related changes in bone marrow and spleen. Blood 2020; 136: 46.
• Schulte-Schrepping J, Reusch N, Paclik D, et al. Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell 2020; 182: 1419-1440.e23.
• Borges I, Sena I, Azevedo P, et al. Lung as a niche for hematopoietic progenitors. Stem Cell Rev Rep 2017; 13: 567-74.
• Lefrançais E, Ortiz-Muñoz G, Caudrillier A, et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature 2017; 544: 105-9.
• Zou Z, Fan X, Liu Y, et al. Endogenous thrombopoietin promotes non-small-cell lung carcinoma cell proliferation and migration by regulating EGFR signalling. J Cell Mol Med 2020; 24: 6644-57.
• Haznedaroğlu IC, Atalar E, Oztürk MA, et al. Thrombopoietin inside the pulmonary vessels in patients with and without pulmonary hypertension. Platelets 2002; 13: 395-9.
• Sim MM, Banerjee M, Hollifield M, et al. Inflammation drives coagulopathies in SARS-CoV-2 Patients. Blood 2020; 136: 34-5.
• Vickers C, Hales P, Kaushik V, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem 2002; 277: 14838-43.
• Abd El-Aziz TM, Al-Sabi A, Stockand JD. Human recombinant soluble ACE2 (hrsACE2) shows promise for treating severe COVID-19. Signal Transduct Target Ther 2020; 5: 258.
• Steckelings UM, Sumners C. Correcting the imbalanced protective RAS in COVID-19 with angiotensin AT2-receptor agonists. Clin Sci (Lond) 2020; 134: 2987-3006.
• Zoufaly A, Poglitsch M, Aberle JH, et al. Human recombinant soluble ACE2 in severe COVID-19. Lancet Respir Med 2020; 8: 1154-8.
• Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020; 181: 905-913.e7.
• Yamamoto K, Takeshita H, Rakugi H. ACE2, angiotensin 1-7 and skeletal muscle: review in the era of COVID-19. Clin Sci (Lond) 2020; 134: 3047-62.
• Rossi GP, Sanga V, Barton M. Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients. Elife 2020; 9: e57278.
• Imanpour H, Rezaee H, Nouri-Vaskeh M. Angiotensin 1-7: a novel strategy in COVID-19 treatment. Adv Pharm Bull 2020; 10: 488-9.
• de Paula Gonzaga ALAC, Palmeira VA, Ribeiro TFS, et al. ACE2/angiotensin-(1-7)/mas receptor axis in human cancer: potential role for pediatric tumors. Curr Drug Targets 2020; 21: 892-901.
• Machado-Silva A, Passos-Silva D, Santos RA, Sinisterra RD. Therapeutic uses for Angiotensin-(1-7). Expert Opin Ther Pat 2016; 26: 669-78.
• Savergnini SQ, Fraga-Silva RA, Ferreira AJ, dos Santos AS. Mas receptor agonists as novel antihypertensive agents. Curr Hypertens Rev 2012; 8: 24-34.
• Santos RAS, Sampaio WO, Alzamora AC, et al. The ACE2/Angiotensin-(1-7)/MAS axis of the renin-angiotensin system: focus on angiotensin-(1-7). Physiol Rev 2018; 98: 505-53.
• Shete A. Urgent need for evaluating agonists of angiotensin-(1-7)/Mas receptor axis for treating patients with COVID-19. Int J Infect Dis 2020; 96: 348-51.
• Magalhaes GS, Rodrigues-Machado MDG, Motta-Santos D, Campagnole-Santos MJ, Santos RAS. Activation of ang-(1-7)/mas receptor is a possible strategy to treat coronavirus (SARS-CoV-2) Infection. Front Physiol 2020; 11: 730.