Modulation of ACE2 in experimental hypertension and in response to treatment with ACE inhibitors and ARBs: potential implications on the severity and therapeutic targets of COVID-19

  • Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP)
  • Total publications:0 publications

Grant number: 2020/05338-3

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2022
  • Known Financial Commitments (USD)

    $14,379.46
  • Funder

    Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP)
  • Principle Investigator

    Pending
  • Research Location

    Brazil, Americas
  • Lead Research Institution

    Universidade de São Paulo
  • Research Category

    Pathogen: natural history, transmission and diagnostics

  • Research Subcategory

    Pathogen morphology, shedding & natural history

  • Special Interest Tags

    Gender

  • Study Subject

    Clinical

  • Clinical Trial Details

    Not applicable

  • Broad Policy Alignment

    Pending

  • Age Group

    Unspecified

  • Vulnerable Population

    Unspecified

  • Occupations of Interest

    Unspecified

Abstract

Clinical evidence indicates that hypertensive patients are highly susceptible to infection and to the severity of COVID-19, a disease caused by the new SARS coronavirus SARS-Cov-2. SARS-Cov-2 requires activation of viral S protein by serineprotease TMPRSS2 and subsequent binding of active S protein to angiotensin-converting enzyme 2 (ECA2) to gain access to lung, heart and kidney cells, among others, in which ECA2 is expressed. ECA2, however, is a crucial enzyme component of the renin angiotensin system (SARS). ACE2 degrades angiotensin II (Ang II), a peptide with multiple actions that can lead to the development of arterial hypertension, and generates angiotensin-1-7 (Ang-1-7), which antagonizes the effects of Ang II. Besides that, experimental and clinical studies suggest that blockade of SARS by ACE inhibitors (ACE inhibitors) and type 1 angiotensin II (ARB) antagonists may increase the abundance of ACE2. Due to the fact that patients with arterial hypertension, among other cardiovascular diseases, are routinely treated with SARS blockers, a number of clinical concerns have arisen regarding the potential increased risk of these patients being infected with SARS-Cov-2. Notably, there are no studies in experimental or human models that have examined the effects of ACEI and ARB on protein abundance and ECA2 activity in the lungs, a possible route of infection. In addition, the effects of ACEI and BRA on the modulation of the serine protease TMPRSS2 in arterial hypertension are totally unknown. Furthermore, there is no information available in the literature to show that hypertension per se or male gender, factors that contribute to the poor prognosis of patients with COVID-19, modulate TMPRSS2. The present study was designed with the purpose of providing scientific evidence on the modulation of circulating and tissue ACE2 in experimental arterial hypertension and in response to ACEI and BRA, in addition to examining the potential involvement of differences between genders. The influence of RAS block, arterial hypertension and sex on the modulation of TMPRSS2 will also be elucidated. (AU) The present study was designed with the purpose of providing scientific evidence on the modulation of circulating and tissue ACE2 in experimental arterial hypertension and in response to ACEI and BRA, in addition to examining the potential involvement of differences between genders. The influence of RAS block, arterial hypertension and sex on the modulation of TMPRSS2 will also be elucidated. (AU) The present study was designed with the purpose of providing scientific evidence on the modulation of circulating and tissue ACE2 in experimental arterial hypertension and in response to ACEI and BRA, in addition to examining the potential involvement of differences between genders. The influence of RAS block, arterial hypertension and sex on the modulation of TMPRSS2 will also be elucidated. (AU)