The Effect of RAAS Blockers on ACE2 Levels
Condition: Renin-Angiotensin System
Study type: Observational

Summary: 
      Blockage of renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme
      inhibitors (ACEI) and angiotensin receptor blockers (ARBs) is considered the first-choice of
      drugs for treatment of hypertension, heart failure and chronic kidney disease However, the
      interplay between RAAS blockers and ACE2 hasn't been fully elucidated SARS-CoV-2 is thought
      to infect host cells through ACE2 to cause coronavirus disease 2019 (COVID-19). Recent
      studies revealed that the spikes of COVID-19 could bind to the surface receptors of sensitive
      cells after contacting the airway surface, which may mediate virus entry into target cells
      and viral replication, and ACE2 might be a mediator of infection (South, Brady et al. 2020).
      Therefore, the imbalance in the RAAS, with a shift towards ACE/Ang II and suppression of
      ACE2/Ang-(1-7), may be an important mediator of COVID-19. To date, conflicting evidences were
      reported linking the use of RAAS blockers and the susceptibility to the virus. However,
      others showed that treatment with an RAAS blockers may downregulate the expression of ACE2
      but have no significant effect on its activity This research importantly aimed to solve this
      important issue by determining the exact association between ARBs and ACE inhibitor and ACE2
      activity and levels on clinical and experimental prospects.
    

Detailed description: 
      Blockage of renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme
      inhibitors (ACEI) and angiotensin receptor blockers (ARBs) is considered the first-choice of
      drugs for treatment of hypertension, heart failure and chronic kidney disease . The classic
      RAAS primarily involves 2 enzymes: renin, which cleaves angiotensinogen to the inactive
      decapeptide angiotensin (Ang) I; and ACE that hydrolyzes Ang I to the octapeptide Ang II, the
      well-known vasopressor agent . In fact, the enzymatic cascade of the RAS encompasses an ACE
      homolog known as ACE2. Whereas, the ACE2-dependent pathways directly yield Ang (1-9) from Ang
      I and degrade Ang II to Ang (1-7), which is vasodilator and acts as a feedback mechanism to
      antagonize the vasopressor effect of Ang II. Indeed, ACE inhibitors effectively attenuate Ang
      II formation and augment the levels of the heptapeptide Ang (1-7) . However, the interplay
      between RAAS blockers and ACE2 hasn't been fully elucidated.

      SARS-CoV-2 is thought to infect host cells through ACE2 to cause coronavirus disease 2019
      (COVID-19). Recent studies revealed that the spikes of COVID-19 could bind to the surface
      receptors of sensitive cells after contacting the airway surface, which may mediate virus
      entry into target cells and viral replication, and ACE2 might be a mediator of infection
      Therefore, the imbalance in the RAAS, with a shift towards ACE/Ang II and suppression of
      ACE2/Ang-(1-7), may be an important mediator of COVID-19. To date, conflicting evidences were
      reported linking the use of RAAS blockers and the susceptibility to the virus. However,
      others showed that treatment with an RAAS blockers may downregulate the expression of ACE2
      but have no significant effect on its activity .

      Furthermore, SARS-CoV-2 infection has largely been influenced by multiorgan involvement
      inducing multiple comorbidities due to the wide distribution of ACE2 thought out the whole
      body. In addition, hypertension, cardiovascular disease, and chronic kidney disease are
      supposed to be potential but unconfirmed risk factors for COVID-19 in adults and children .
      However, the expression of ACE2 may be lower in patients with hypertension than in people
      with normal blood pressure . Concluding more conflicting evidences for the association of
      COVID-19 with RAAS inhibitors.

      Given the RAAS importance to cardiovascular and kidney physiology, and the association
      between chronic diseases and COVID-19, could shed light on potential relationships between
      ACE inhibitor and ARB use and COVID-19.

      Accordingly, evidences are required to solve the question of whether ARBs and ACE inhibitor
      have either favorable or harmful effects on the susceptibility to SARS-CoV-2 in addition to
      the severity and outcomes of COVID-19 infection. This research importantly aimed to solve
      this important issue by determining the exact association between ARBs and ACE inhibitor and
      ACE2 activity and levels on clinical and experimental prospects.
    

Intervention name(s): ACE inhibitor ,angiotensin receptor blockers
Intervention type(s): Drug
Intervention description(s): patients taking ACEI or ARBs with cardiovascular disease
Intervention MeSH terms: Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists
Observational model: Other
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        patients with controlled Hypertension or heart failure presenting to Cardiac Rehabilitation
        Units taking ACE inhibitors or AGII blockers