Skip to main content
SpringerLink
Log in

Panendothelitis Due to the SARS COV 2 Infection: Consequences on Hypertension and Heart Failure

  • Chapter
  • First Online:
Hypertension and Heart Failure

Part of the book series: Updates in Hypertension and Cardiovascular Protection ((UHCP))

  • 119 Accesses

Abstract

SARS-Cov-2 is the seventh known coronavirus to infect the human species3. It is impossible to say that the virus is the result of natural evolution and selection or is actually the result of multiple passages (in vitro or in vivo). SARS-CoV-2 has a genomic sequence that is 89% identical to SARS-Cov and 50% identical to MERS. Genomic features can only partially explain the transmissibility of SARS-Cov-2 in humans, as per the authors cited above [1]. It is stated in the before-mentioned article that the evidence showing that it is not a deliberately manipulated virus is practically impossible to confirm, as it is impossible to disprove the theories regarding the origin of the virus in question. The acquisition of both the polybasic cleavage site and the prediction of O-linked glycans is arguments against scenarios based on the current scientific culture.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    PRRS: Pattern recognition receptors and induces the innate immune response.

    NLRP3: Critical component of the innate immune system (intracellular sensor protein) which controls the secretion of proinflammatory interleukins in response to infections and cell damage.

  2. 2.

    MAPK—Mitogen-activated protein kinase.

    TLR2—Toll-type receiver 2, located membrane recognizes lipoproteins from pathogens (bacteria, viruses, fungi, etc.) and signals the production of proinflammatory cytokines.

  3. 3.

    MAPK—Mitogen-activated protein kinase.

    TLR2—Toll-type receiver 2, located membrane recognizes lipoproteins from pathogens (bacteria, viruses, fungi, etc.) and signals the production of proinflammatory cytokines.

References

  1. Andersen K, et al. The proximal origin of SARS-Cov-2. Nat Med. 2020;26:450–2.

    Article  CAS  Google Scholar 

  2. McIntyre CR, et al. Converging and emerging threat to health security. Environ Syst Decis. 2018;38:198–207.

    Article  Google Scholar 

  3. Imai Y, et al. Angiotensin-converting enzyme (ACE2) in disease pathogenesis. Circ J. 2010;74:105–410.

    Article  Google Scholar 

  4. Imai Y, et al. Angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Cell Mol Life Sci. 2007;64:2006–12.

    Article  CAS  Google Scholar 

  5. Imai Y, et al. Angiotensin-converting enzyme protects from severe acute lung failure. Nature. 2005;436:112–6. https://doi.org/10.1038/nature03712.

    Article  CAS  Google Scholar 

  6. Matsuyama S, et al. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by transmembrane protease TMPRSS2. J Virol. 2010;84:12658–64.

    Article  CAS  Google Scholar 

  7. Zhou F, et al. Clinical course and risk factors for mortality of adult inpatients with Covid-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.

    Article  CAS  Google Scholar 

  8. Saif LJ. Animal coronaviruses: lessons for SARS. Washington, DC: National Academic Press; 2004.

    Google Scholar 

  9. Voicu V, Cernescu C, Popescu I. Pandemia Covid-19 în Romania. In: Aspecte clinice și epidemiologice. București: Editura Academiei Române; 2020.

    Google Scholar 

  10. Hoffman M, et al. SARS-Cov-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by clinical proven protease inhibitor. Cell. 2020;181:271–280.e8.

    Article  Google Scholar 

  11. Wrapp D, et al. Cryo-EM structure of the 2019-n Cov spike in the prefusion conformation. Science. 2020;367:1260–3.

    Article  CAS  Google Scholar 

  12. Gibson P, et al. Covid-19 acute respiratory distress syndrome (ARDS) clinical features and differences from typical pre-Covid-19 ARDS. Med J Aust. 2020;213:54–56.e1. https://doi.org/10.5694/mja2.50674.

    Article  Google Scholar 

  13. Lippi G, et al. Coronavirus disease 2019 (Covid-19) the portrait of perfect storm. Ann Transl Med. 2020;8:497.

    Article  CAS  Google Scholar 

  14. Lippi G, et al. Covid-19: unravelling the clinical progression of nature’s virtually perfect biological weapon. Ann Transl Med. 2020;8(11):693.

    Article  CAS  Google Scholar 

  15. Harrison A, et al. Mechanisms of SARS-Cov-2 transmission and pathogenesis. Trends Immunol. 2020;41(12):1100–14.

    Article  CAS  Google Scholar 

  16. Lippi G, et al. Coronavirus disease 2019 (Covid-19): the portrait of a perfect storm. Ann Transl Med. 2020;8(7):497. https://doi.org/10.21037/atm.2020.03.157.

    Article  CAS  Google Scholar 

  17. Voicu V. SARS-Cov-2, ACE2, panendothelitis and viral neuroinvasion. Systemic consequences. J Hypertens Res. 2021;7(1):4–11.

    Google Scholar 

  18. Jha NK, et al. Current understanding of novel Coronavirus: molecular pathogenesis diagnosis and treatment approaches. Immuno. 2021;1:30–66.

    Article  Google Scholar 

  19. Hamming I, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS-coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631–7.

    Article  CAS  Google Scholar 

  20. Voicu V. Mecanisme patogenice în infecția cu virusul SARS-Cov-2. SARS-Cov-2-receptor, penetrarea în celula umană, patogenie, mecanisme. In: Voicu V, Cernescu C, Popescu I, editors. Patogenia Covid-19 în Romania, aspecte clinice și epidemiologice. București: Editura Academiei Române; 2020.

    Google Scholar 

  21. Voicu V. The impact of SARS-Cov-2 infection on the renin-angiotensin-aldosterone system and its axes. Pathogenic consequences. J Hypertens Res. 2020;6(4):99–110.

    Google Scholar 

  22. Voicu V. SARS-Cov-2, ACE2, panendothelitis and viral neuro-invasion. Systemic consequences. J Hypertens Res. 2021;7(1):4–12.

    Google Scholar 

  23. Saponaro F, et al. ACE2 in the era of SARS-Cov-2: controversies and novel perspectives. Front Mol Biosci. 2020;7:588618.

    Article  CAS  Google Scholar 

  24. Grasselli G, et al. Baseline characteristics and outcome of 1591 patients infected with SARS-Cov-2 admitted to ICUs of the Lombardi region, Italy. JAMA. 2020;323:1574–81.

    Article  CAS  Google Scholar 

  25. Gheblawi M, et al. Angiotensin-converting enzyme 2: SARS-Cov-2 receptor and regulator of the renin-angiotensin system. Circ Res. 2020;126:1457–75.

    Article  Google Scholar 

  26. Rajendran P, et al. The vascular endothelium and human disease. Int J Biol Sci. 2013;9:1057–69.

    Article  CAS  Google Scholar 

  27. Lang M, et al. Pulmonary vascular manifestations of Covid-19 pneumonia. Radiol Cardiothorac Imaging. 2020;2(3):e200277.

    Article  Google Scholar 

  28. Evans PC, et al. Endothelial injury and dysfunction in Covid-19. Cardiovasc Res. 2020;116(14):2177–84.

    Article  CAS  Google Scholar 

  29. Hayashi T, et al. Highly conserved binding region of ACE2 as a receptor for SARS-Cov-2 between human and animals. Vet Q. 2020;40(1):243–9.

    Article  CAS  Google Scholar 

  30. Choi J-Y, et al. Altered Covid-19 receptor ACE2 expression in a higher risk group for cerebrovascular disease and ischemic stroke. Biochem Biophys Res Commun. 2020;528:413–9.

    Article  CAS  Google Scholar 

  31. Cuervo NZ, et al. ACE2: evidence of role as entry receptor for SARS-Cov-2 and implications in comorbidities. Elife. 2020;9:e61390. https://doi.org/10.7554/eLife.61390.

    Article  CAS  Google Scholar 

  32. Devaux C, et al. Can ACE2 receptor polymorphism predict species susceptibility to SARS-Cov-2. Front Public Health. 2021;8:6087665.

    Article  Google Scholar 

  33. Shang J, et al. Structural basis of receptor recognition by SARS-Cov-2. Nature. 2020;581:221–4.

    Article  CAS  Google Scholar 

  34. Yan R, et al. Structural basis for the recognition of the SARS-Cov-2 by full-length human ACE2. Science. 2020;367:1444–8.

    Article  CAS  Google Scholar 

  35. Bakhshandeh B, et al. Variants in ACE2 potential influences on virus infection and Covid-19 severity. Infect Genet Evol. 2021;90:104773.

    Article  CAS  Google Scholar 

  36. Qui H, et al. Clinical and epidemiological feature of 36 children with coronavirus disease 2019 (Covid-19) in Zhejiang, China: on observational study. Lancet Infect Dis. 2020;20:689–96.

    Article  Google Scholar 

  37. Benetti E, et al. ACE2 gene variants may underlie interindividual variability and susceptibility to Covid-19 in the Italian population. Eur J Hum Genet. 2020;28:1602–14.

    Article  CAS  Google Scholar 

  38. Re R, et al. Estimating the reproductive number Ro of SARS-Cov-2 in the United State and eight European countries and implication for vaccination. J Theor Biol. 2021;517:110621.

    Article  Google Scholar 

  39. Beyerstedt S, et al. Covid-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-Cov-2 infection. Eur J Clin Microbiol Infect Dis. 2021;40:905–19. https://doi.org/10.1007/s10096-020-04138-6.

    Article  CAS  Google Scholar 

  40. Nguyen HL, et al. Does SARS-Cov-2 bind to human ACE2 more strongly than does SARS-Cov? J Phys Chem. 2020;124:7336–47.

    Article  CAS  Google Scholar 

  41. Rodrigues R, et al. The impact of ACE2 expression levels in patients with comorbidities on Covid-19 severity: a comprehensive review. Microorganisms. 2021;9:1692.

    Article  CAS  Google Scholar 

  42. Zou X, et al. 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;14:185–92.

    Article  Google Scholar 

  43. Li Y, et al. Molecular mechanisms of sex bias differences in Covid-19 mortality. Crit Care. 2020;24:405.

    Article  Google Scholar 

  44. Kornilov SA, et al. Plasma level of soluble ACE2 are associated with sex, metabolic syndrome, and its biomarkers in a large cohort, pointing to a possible mechanisms for increased severity in Covid-19. Crit Care. 2020;24:452.

    Article  Google Scholar 

  45. Varga Z. Endothelial cell infection and endothelitis in Covid-19. Lancet. 2020;395:1417–8.

    Article  CAS  Google Scholar 

  46. Labo N, et al. Vasculopathy and coagulopathy associated with SARS-Cov-2 infection. Cell. 2020;9:1583.

    Article  CAS  Google Scholar 

  47. Almashat SA. Vasculitis in Covid-19: a literature review. J Vasculitis. 2020;6:1. https://doi.org/10.37421/JOV.2020.6.129.

    Article  Google Scholar 

  48. Gavrilaki E, et al. Endothelial dysfunction in Covid-19: lessons learned from coronaviruses. Curr Hypertens Rep. 2020;22:63.

    Article  Google Scholar 

  49. Del Turco S, et al. Covid-19 and cardiovascular consequences: is the endothelial dysfunction the hardest challenge? Thromb Res. 2020;196:143–51.

    Article  Google Scholar 

  50. Calabrese F, et al. Pulmonary pathology and Covid-19: lesson from autopsy. The experience of European pulmonary pathologists. Virchows Arch. 2020;477:359–72. https://doi.org/10.1007/s00428-020-02886-6.

    Article  CAS  Google Scholar 

  51. Voicu V. Post-Covid-19 sequelae or persistent Covid-19 disease. J Hypertens Res. 2021;7(3):84–8.

    Google Scholar 

  52. Voicu V. Sechele post-Covid-19 sau Boala post-Covid-19 prelungită (Sindromul post-Covid-19). București: Editura Academiei Române; 2021.

    Google Scholar 

  53. Jung F, et al. Covid-19 and the endothelium. Clin Hemorheol Microcirc. 2020;75:7–11.

    Article  CAS  Google Scholar 

  54. Perico L, et al. Immunity, endothelial injury and complement-induced coagulopathy in Covid-19. Nat Rev Nephrol. 2020;17:46–64. https://doi.org/10.1038/s41581-020-00357-4.

    Article  Google Scholar 

  55. Aird WC. Endothelium in health and disease. Pharmacol Rep. 2008;60:139–43.

    Google Scholar 

  56. Ludmer PL, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986;315:1046–51.

    Article  CAS  Google Scholar 

  57. Gimbrone MA Jr. Endothelial dysfunction and the pathogenesis of atherosclerosis. New York: Springer Verlag; 1980.

    Book  Google Scholar 

  58. Cybulsky MI, et al. Endothelial expression of a mononuclear leucocyte adhesion molecule during atherosclerosis. Science. 1991;251:788–91.

    Article  CAS  Google Scholar 

  59. Furchgott RF, et al. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–6.

    Article  CAS  Google Scholar 

  60. Celermajer D. Endothelial dysfunction: does it matter? Is it reversible? J Am Coll Cardiol. 1997;30:325–33.

    Article  CAS  Google Scholar 

  61. Maccio U, et al. SARS-Cov-2 leads to a small vessel endotheliitis in the heart. Ebio Medicine. 2021;63:103182.

    CAS  Google Scholar 

  62. Maccio U, et al. SARS-Cov-2 leads to a small vessel endotheliitis in the heart. EBioMedicine. 2021;63:103182.

    Article  CAS  Google Scholar 

  63. Huertas A, et al. Endothelial cell dysfunction: a major player in SARS-Cov-2 infection? Eur Respir J. 2020;54:2001634.

    Article  Google Scholar 

  64. Huertas A, et al. Endothelial cell dysfunction: a major player in SARS-Cov-2 infection (Covid-19?). Eur Respir J. 2001;2020(56):634.

    Google Scholar 

  65. Nicosia R, et al. Covid-19 vasculopathy: mounting evidence for the indirect mechanism of endothelial injury. Am J Pathol. 2021;191(8):1374–84.

    Article  CAS  Google Scholar 

  66. Libby P, Lüscher T. Covid-19 is, in the end, an endothelial disease. Eur Heart J. 2020;41:3038–44.

    Article  CAS  Google Scholar 

  67. Hamming I, et al. The emerging role of ACE2 in physiology and pathology. J Pathol. 2007;212:1–11.

    Article  CAS  Google Scholar 

  68. Basta G. Direct or indirect endothelial damage? An unresolved question. EBioMedicine. 2021;64:103215.

    Article  CAS  Google Scholar 

  69. Teuwen L-A, et al. Covid-19: the vasculature unleashed. Nat Rev Immunol. 2020;20:389–91.

    Article  CAS  Google Scholar 

  70. Pons S, et al. The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-Cov-2 infection. Crit Care. 2020;24(353):1–8.

    Google Scholar 

  71. Pons S, et al. The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-Cov-2 infection. Crit Care. 2020;24:353.

    Article  Google Scholar 

  72. Kaur S, et al. The enigma of endothelium in Covid-19. Front Physiol. 2020;11:989.

    Article  Google Scholar 

  73. Sudano I, et al. Protection of endothelial function: targets for nutritional and pharmacological intervention. J Cardiovasc Pharmacol. 2006;47(Suppl 2):S-136–S150.

    Article  CAS  Google Scholar 

  74. Su JB. Vascular endothelial dysfunction and pharmacological treatment. World J Cardiol. 2015;7(11):719–41.

    Article  Google Scholar 

  75. O’Sullivan J, et al. Endothelial cells orchestrate Covid-19. Lancet Hematol. 2020;7(8):e553–5. https://doi.org/10.1016/s2352-3026(20)30215-5.

    Article  Google Scholar 

  76. Bikdeli B, et al. Covid-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy and fellow up, JAAC State of the art review. J Am Coll Cardiol. 2020;75(23):2950–73.

    Article  CAS  Google Scholar 

  77. Brunner H, et al. Endothelial function and dysfunction. Part II: association with cardiovascular risk factors and disease. A statement of the working group on endothelins and endothelial factors of European Society of Hypertension. J Hypertens. 2005;23:233–46.

    Article  CAS  Google Scholar 

  78. Liu F, et al. SARS-Cov-2 infects endothelial cells in vivo and in vitro. Front Cell Infect Microbiol. 2021;11:701278.

    Article  CAS  Google Scholar 

  79. Peiris S, et al. Pathological findings in organs and tissue of patients with Covid-19: a systematic review. PLoS One. 2021;16:e0250708. https://doi.org/10.1371/journal.pone.0250708.

    Article  CAS  Google Scholar 

  80. Amraei R, et al. Covid-19, renin-angiotensin system and endothelial dysfunction. Cell. 2020;9:1652.

    Article  CAS  Google Scholar 

  81. Ackermann M, et al. Pulmonary vascular endothelitis, thrombosis and angiogenesis in Covid-19. N Engl J Med. 2020;383:120–8.

    Article  CAS  Google Scholar 

  82. Ashrof UM, et al. SARS-Cov-2, ACE2 expression, and systemic organ invasion. Physiol Genomics. 2021;53:51–60.

    Article  Google Scholar 

  83. Xia H, et al. Brain angiotensin-converting enzyme type 2 shedding contributes to the development of neurogenic hypertension. Circ Res. 2013;113:1087–96.

    Article  CAS  Google Scholar 

  84. Stein R, et al. From ACE2 to Covid-19: a multiorgan endothelial disease (editorial). Int J Infect Dis. 2020;100:425. https://doi.org/10.1016/J.iJid.2020.08.083.

    Article  CAS  Google Scholar 

  85. Leisman D, et al. Facing Covid-19 in the ICU: vascular dysfunction, thrombosis and dysregulated inflammation. Intensive Care Med. 2020;46:1105–68.

    Article  CAS  Google Scholar 

  86. Gomes Silva IV, et al. Effects of different classes of antihypertensive drugs on endothelial function and inflammation. Int J Mol Sci. 2019;20(3458):9–15.

    Google Scholar 

  87. Cameron AC, et al. Drug treatment of hypertension: focus on vascular health. Drugs. 2016;76:1529–50.

    Article  CAS  Google Scholar 

  88. Wu Z, et al. Elevation of plasma angiotensin II level is a potential pathogenesis for the critical ill Covid-19 patients version 2. Crit Care. 2020;24:290.

    Article  Google Scholar 

  89. Wu Z, et al. Characteristics of and important lessons from coronavirus disease (Covid-19) outbreak in China: summary of a report of 72314 cases from Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239–42.

    Article  CAS  Google Scholar 

  90. Le SJ, et al. Coronavirus: innate immunity, inflammasome activation, inflammatory cell death and cytokines. Trends Immunol. 2020;41:1083–99.

    Article  Google Scholar 

  91. Bergsbaken T, et al. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol. 2009;7:99–109.

    Article  CAS  Google Scholar 

  92. Yan L, et al. An interpretable mortality prediction model for Covid-19 patients. Nat Mach Intell. 2020;2:283–8.

    Article  Google Scholar 

  93. Christgen S, et al. Identification of the PANoptosome a molecular platform trigering pyroptosis, apoptosis and necroptosis (PANaptosis). Front Cell Infect Microbiol. 2020;10:237.

    Article  CAS  Google Scholar 

  94. Heiling R, et al. Function and mechanism of the pyrin inflammasome. Eur J Immunol. 2018;18:230–8.

    Article  Google Scholar 

  95. Schnappauf O, et al. The pyrin inflammasome in health and disease. Front Immunol. 2019;10:1745.

    Article  CAS  Google Scholar 

  96. Zahid A, et al. Pharmacological inhibitors of the NIRP3 inflammasome. Front Immunol. 2019;10:2538.

    Article  Google Scholar 

  97. Zu ZY, et al. Coronavirus disease 2019 (Covid-19): a perspective from China. Radiology. 2020;296:E15–25.

    Article  Google Scholar 

  98. Knowlton K. Pathogenesis of SARS-Cov-2 induced cardiac injury from perspective of the virus. J MolCellCardiol. 2020;147:12–7.

    CAS  Google Scholar 

  99. Tomasoni D, et al. Covid-19 and heart failure: from infection to inflammation and angiotensin II stimulation, searching for evidence from a new disease. Eur J Heart Fail. 22:957–66.

    Google Scholar 

  100. Yang J, et al. Prevalence of comorbidities and its effects in patients infected with SARS-Cov-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91–5.

    Article  CAS  Google Scholar 

  101. Hu Y, et al. Prevalence and severity of coronavirus disease 2019 (Covid-19): a systematic review and meta-analysis. J Clin Virol. 2020;127:104371.

    Article  CAS  Google Scholar 

  102. Veluswami P, et al. The SARS-Cov-2/receptor axis in heart and blood vessels: a crisp update on Covid-19 disease with cardiovascular complications. Viruses. 2021;13:1346.

    Article  Google Scholar 

  103. Fu L, et al. Prevalence and impact of cardiac injury on Covid-19. A systematic review and meta-analysis. Clin Cardiol. 2021;44:276–83.

    Article  Google Scholar 

  104. Shibata S, et al. Hypertension and related diseases in the era of Covid-19: a report from the Japanese Society of hypertension task force on Covid-19. Hypertens Res. 2020;43:1028–46.

    Article  CAS  Google Scholar 

  105. Anderson TJ, et al. Close relation of endothelial function in the human coronary and peripheral circulation. J Am Coll Cardiol. 1995;26:1235–41.

    Article  CAS  Google Scholar 

  106. Little PJ, et al. Endothelial dysfunction and cardiovascular disease: history and analysis of the clinical utility of the relationship. Biomedicine. 2021;9:699.

    CAS  Google Scholar 

  107. Rodriguez R, et al. The impact of ACE2 expression levels in patients with comorbidities on Covid-19 severity: a comprehensive review. Microorganisms. 2021;9:1692.

    Article  Google Scholar 

  108. Liang C, et al. The ACE2 expression in human heart indicates new potential mechanisms of heart injury among patients infected with SARS-Cov-2. Cardiovasc Res. 2020;116:1097–100.

    Article  Google Scholar 

  109. Nishiga M, et al. Covid-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol. 2020;17:543–58.

    Article  CAS  Google Scholar 

  110. Gu SX, et al. Thrombocytopathy and endotheliopathy: crucial contributors to Covid-19 thromboinflammation. Nat Rev Cardiol. 2021;18:194–209.

    Article  CAS  Google Scholar 

  111. Smadja D, et al. Angiopoietin-2 as a marker of endothelial activation is a good predictor factor Covid-19 patients. Angiogenesis. 2020;23:611–20. https://doi.org/10.1007/s10456-020-09730-0.

    Article  CAS  Google Scholar 

  112. Dupont A, et al. Vascular endothelial damage in the pathogenesis of organ injury in severe Covid-19. Arterioscler Thromb Vasc Biol. 2021;41:1760–73.

    Article  CAS  Google Scholar 

  113. Calvo-Fernandez A, et al. Markers of myocardial injury in the prediction of short Covid-19 prognosis. Rev Esp Cardiol (Engl Ed). 2021;74(7):576–83.

    Google Scholar 

  114. Shi S, et al. Association of cardiac injury with mortality in hospitalized patients with Covid-19, in Wuhan, China. JAMA Cardiol. 2020;5(7):802–10.

    Article  Google Scholar 

  115. Giustino G, et al. Coronavirus and cardiovascular disease, myocardial injury and arrhythmia: JACC focus seminar. J Am Coll Cardiol. 2020;76(17):2011–23.

    Article  CAS  Google Scholar 

  116. Narita K, et al. Disaster hypertension and cardiovascular events in disaster and Covid-19 pandemic. J Clin Hypertens. 2021;23:575–83.

    Article  CAS  Google Scholar 

  117. Narita K, et al. Time course of disaster related cardiovascular disease and blood pressure elevation. Hypertens Res. 2021;44:1534–9.

    Article  Google Scholar 

  118. Bastola U. Is Covid-19 severity associated with ACE2 degradation. Front Drug Discov. 2021. https://arxiv.org.

  119. Zisman LS, et al. Increased angiotensin (1-7) forming activity in human heart ventricles. Evidence for upregulation of angiotensin-converting enzyme homologue ACE2. Circulation. 2003;108:1707–12.

    Article  CAS  Google Scholar 

  120. Goulter AB, et al. ACE2 gene expression is up-regulated in human heart failing. BMC Med. 2004;2:19.

    Article  Google Scholar 

  121. Ramos SG, et al. ACE2 down-regulation may act as a transient molecular disease causing RAAS dysregulation and tissue damage in the microcirculatory environment among Covid-19 patients. Am J Pathol. 2021;191:1154–64.

    Article  CAS  Google Scholar 

  122. Saba L, et al. Molecular pathway triggered by Covid-19 in different organs: ACE2 receptor expressing, cells under attack? A review. Eur Rev Med Pharmacol Sci. 2020;24(23):12609–22.

    CAS  Google Scholar 

  123. Jeffers SA, et al. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. PNAS. 2004;101:15748–53.

    Article  CAS  Google Scholar 

  124. Giordo R, et al. SARS-Cov-2 and endothelial cell interaction in Covid-19: molecular perspectives. Vasc Biol. 2021;3:R15–23. https://doi.org/10.1530/VB-20-0017.

    Article  CAS  Google Scholar 

  125. Daly JL, et al. Neuropilin-1 is a host factor for SARS-Cov-2 infection. Science. 2020;370:861–5.

    Article  CAS  Google Scholar 

  126. Cantuti-Castelvetri L, et al. Neuropilin-1 facilitates SARS-Cov-2 cell entry and provides a possible pathway into the central nervous system. bioRxiv. 2020. https://doi.org/10.1101/2020.06.07.137802.

  127. Perez-Bermejo JA, et al. SARS-Cov-2 infection of human iPSC-derived cardiac cell reflects cytopathic features in hearts of patients with Covid-19. Sci Transl Med Res. 2021;13:eabf7872.

    Article  CAS  Google Scholar 

  128. Qian Y, et al. Direct activation of endothelial cells by SARS-Cov-2 nucleocapsid protein is blocked by simvastatin. J Virol. 2021;95(23):e01396–21.

    Article  CAS  Google Scholar 

  129. Zheng M, et al. TLR2, senses the SARS-Cov-2 envelope protein to produce inflammatory cytokines. Nat Immunol. 2021;22:829–33.

    Article  CAS  Google Scholar 

  130. Li T, et al. Serum SARS-Cov-2 nucleocapsid protein: a sensitivity and specificity early diagnostic marker for SARS-Cov-2 infection. Front Cell Infect Microb. 2020;10:470. https://doi.org/10.3389/fcimb.2020.00470.

    Article  CAS  Google Scholar 

  131. Cenko E, et al. Cardiovascular disease and Covid-19: a consensus paper from ESC Working group on coronary pathophysiology & circulation, ESC Working group on thrombosis and the association for acute cardiovascular care, in collaboration with European Heart Rhythm Association (EHRA). Cardiovasc Res. 2021;117:2705–29.

    Article  CAS  Google Scholar 

  132. Ruan Q, et al. Clinical predictors of mortality due to Covid-19 based on analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846–8.

    Article  CAS  Google Scholar 

  133. Lei Y, et al. SARS-Cov-2 spike protein impairs endothelial function via downregulation of ACE2. Circ Res. 2021;128:1323–6.

    Article  CAS  Google Scholar 

  134. Mackman N. Role of tissue factor in hemostasis, thrombosis and vascular development. Atheroscler Thromb Vasc Biol. 2004;24:1015–22.

    Article  CAS  Google Scholar 

  135. Zheng Y-Y, et al. Covid-19 and the cardiovascular system. Nat Rev. 2020;17:259–60.

    CAS  Google Scholar 

  136. Bader F, et al. Heart failure and Covid-19. Heart Fail Rev. 2020;26:1–10. https://doi.org/10.1007/s10741-020-10008-2.

    Article  CAS  Google Scholar 

  137. Bonaventura A, et al. Endothelial disfunction and immunothrombosis as key pathogenic mechanisms in Covid-19. Nat Rev. 2021;21:319–28.

    CAS  Google Scholar 

  138. Prescott H, et al. Recovery from severe Covid-19: Leveraging the lessons survival from sepsis. JAMA. 2020;324(8):739.

    Article  Google Scholar 

  139. Yan LM, et al. SARS-Cov-2 is an unrestricted bioweapon: a truth revealed through uncovering a large-scale, organised scientific fraud. https://doi.org/10.5281/zenoda.4073131.svg.

  140. Jain R, et al. SARS-Cov-2 pandemic: a critical review on novel coronavirus pathogenesis, clinical diagnosis and treatment. J Drug Deliv Therap. 2020;10(3):241–52.

    Article  CAS  Google Scholar 

  141. Ben H, et al. Characteristics of SARS-Cov-2 and Covid-19. Nat Rev Microbiol. 2020;19:141–54. https://doi.org/10.1038/s41579-020-00459-7.

    Article  CAS  Google Scholar 

  142. Tang D, et al. The hallmarks of Covid-19 disease. PLoS Pathog. 2020;16:e1008536. https://doi.org/10.1371/journal.ppat.1008536.

    Article  CAS  Google Scholar 

  143. Kai H, et al. Interaction of coronavirus with ACE2, angiotensin II and RAS inhibitors-lessons from available evidence and insight into Covid-19. Hypertens Res. 2020;43:648–54. https://doi.org/10.1038/s41440-020-0455-8.

    Article  CAS  Google Scholar 

  144. Bourgonje A, et al. Angiotensin-converting enzyme 2 (ACE2), SARS-Cov-2 and the pathophysiology of coronavirus disease 2019 (Covid-19). J Pathol. 2020;251:228–48.

    Article  CAS  Google Scholar 

  145. Glowacka I, et al. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduce, viral control by the humoral immune response. J Virol. 2011;85:4122–34.

    Article  Google Scholar 

  146. Synowiec A, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2): a systemic infection. Clin Microbiol Rev. 2021;34(2):e00133–20.

    Article  CAS  Google Scholar 

  147. Pinto P, et al. ACE2 expression is increased in the lungs of patients with comorbidities associated with severe Covid-19. J Infect Dis. 2020;222:556. https://doi.org/10.1093/infectis/jiaa.

    Article  CAS  Google Scholar 

  148. Khayat AS, et al. ACE2 polymorphisms as potential players in Covid-19 outcome. PLoS One. 2020;15:e0243887. https://doi.org/10.1371/journal.pone.0243887.

    Article  CAS  Google Scholar 

  149. Yuen K-S, et al. SARS-Cov-2 and Covid-19: the most important research questions. Cell Biosci. 2020;10:40. https://doi.org/10.1186/s13578-020-00404-4.

    Article  CAS  Google Scholar 

  150. Wang J, et al. Molecular simulation of SARS-Cov-2 spike protein binding to pangolin ACE2 or human ACE2 natural variants reveals altered susceptibility to infection. J Gen Virol. 2020;101:921–4.

    Article  CAS  Google Scholar 

  151. Sivaraman H, et al. Structural basis of SARS-Cov-2 and SARS-Cov receptor binding and small molecule blockers as potential therapeutics. Annu Rev Pharmacol Toxicol. 2021;71:465–93.

    Article  Google Scholar 

  152. Sims J, et al. Characterization of the cytokine storm—reflects hyperinflammatory endothelial dysfunction in Covid-19. J Allergy Clin Immunol. 2021;147:107–11. https://doi.org/10.1016/J.Jaci.2020.08.031.

    Article  CAS  Google Scholar 

  153. Aird WC. Mechanisms of endothelial cell heterogeneity in health and disease. Circ Res. 2006;98:159–62.

    Article  CAS  Google Scholar 

  154. Celermajep D, et al. Endothelial dysfunction: does it matter? It is reversible? J Am Coll Cardiol. 1997;30(2):325–33.

    Article  Google Scholar 

  155. Gladka M, et al. The endothelium as Achilles’ heel in Covid-19 patients. Cardiovasc Res. 2020;116(14):e195–7.

    Article  CAS  Google Scholar 

  156. Thomas PG, et al. The intracellular sensor NLRP3 mediates key innate and healing responses in influenza a virus via the regulation of caspase-1. Immunity. 2009;30:566–75.

    Article  CAS  Google Scholar 

  157. Nieto-Torres JL, et al. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity pronates virus fitness and pathogenesis. PLoS Pathog. 2014;10:e1004077.

    Article  Google Scholar 

  158. Vardecchia P, et al. The pivotol link between ACE2 deficiency and SARS-Cov-2 infection. Eur J Intern Med. 2020;76:14–20.

    Article  Google Scholar 

  159. Pasparakis M, et al. Necroptosis and its role in inflammation. Nature. 2015;517:311–20.

    Article  CAS  Google Scholar 

  160. Zheng M, et al. Caspase-6 is a key regulator of innate immunity, inflammasome activation and host defense. Cell. 2020;181:674–687.e13.

    Article  CAS  Google Scholar 

  161. Patak EM. Convalescent plasma is ineffective for Covid-19. BMJ. 2020;371:m4072.

    Article  Google Scholar 

  162. Widlansky M, et al. The clinical implications of endothelial dysfunctions. J Am Coll Cardiol. 2003;42(7):1149–60.

    Article  CAS  Google Scholar 

  163. Al-Farabi MJ, et al. Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (Covid-19) patients: a systematic review and meta-analysis. Microvasc Res. 2021;138:104224.

    Article  Google Scholar 

  164. Banon-Gonzales R, et al. Autopsies of suspected SARS-Cov-2 cases. Spanish J Legal Med. 2020;46(3):93–100.

    Article  Google Scholar 

  165. Umbrajkar S, et al. Cardiovascular health and disease in the context of Covid-19. Cardiol Res. 2021;12(2):67–79.

    Article  Google Scholar 

  166. Farshidfar F. Cardiovascular complication of Covid-19. JCI Insight. 2021;6(13):e148980.

    Article  Google Scholar 

  167. Manganaro R, et al. Endothelial dysfunction and coronary artery disease: new insight from reactive hyperemia test. Vessel Plus. 2021;1(5):37.

    Google Scholar 

  168. van Eijk LE, et al. Covid-19: immunopathology, pathophysiological mechanism and treatment option. J Pathol. 2021;254:307–31.

    Article  Google Scholar 

  169. Amraei R, et al. CD209L/L-SIGN and CD209/DC-SIGN act as receptor for SARS-Cov-2 and are differentially expressed in lung and kidney epithelial and endothelial cells. bioRxiv. 2020. https://doi.org/10.1101/2020.06.22.165803

  170. Chen L, et al. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-Cov-2. Cardiovasc Res. 2020;116:1097–110.

    Article  CAS  Google Scholar 

  171. Xudong X, et al. Age-and gender related difference of ACE2 expression in rat lung. Life Sci. 2006;78:2166–71.

    Article  Google Scholar 

  172. McFadyen JD, et al. The emerging threat of (micro) thrombosis in Covid-19 and its therapeutic implications. Circ Res. 2020;127:571–87.

    Article  CAS  Google Scholar 

  173. Mehra MR, et al. Cardiovascular disease, drug therapy and mortality in Covid-19. N Engl J Med. 2020;382(25):e102.

    Article  CAS  Google Scholar 

  174. Voicu V. Post-Covid-19 sequellae or persistent Covid-19 disease. J Hypertens. 2021;7(3):84–8.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Toxicology and Clinical Psychopharmacology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

    Victor Voicu

Authors
  1. Victor Voicu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Carol Davila University of Medicine and Pharmacy, Bucharest, Bucuresti, Romania

    Maria Dorobantu

  2. Department of Pharmacology, Toxicology and Clinical Psychopharmacology Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

    Victor Voicu

  3. University of Milano-Bicocca, Milano, Italy

    Guido Grassi

  4. Dept of Clinical and Experimental Sci, University of Brescia, Brescia, Italy

    Enrico Agabiti-Rosei

  5. University of Milano-Bicocca, Milano, Italy

    Giuseppe Mancia

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Voicu, V. (2023). Panendothelitis Due to the SARS COV 2 Infection: Consequences on Hypertension and Heart Failure. In: Dorobantu, M., Voicu, V., Grassi, G., Agabiti-Rosei, E., Mancia, G. (eds) Hypertension and Heart Failure. Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-031-39315-0_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-39315-0_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-39314-3

  • Online ISBN: 978-3-031-39315-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation