COVID-19 and renin-angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) - Is there any scientific evidence for controversy?

Abstract

Renin-angiotensin system (RAS) blockers are extensively used worldwide to treat many cardiovascular disorders, where they are effective in reducing both mortality and morbidity. These drugs are known to induce an increased expression of angiotensin-converting enzyme 2 (ACE2). ACE2 acts as receptor for the novel SARS coronavirus-2 (SARS-CoV-2) which raising the important issue of possible detrimental effects that RAS blockers could exert on the natural history and pathogenesis of the coronavirus disease-19 (COVID-19) and associated excessive inflammation, myocarditis and cardiac arrhythmias. We review the current knowledge on the interaction between SARS-CoV-2 infection and RAS blockers and suggest a scientific rationale for continuing RAS blockers therapy in patients with COVID-19 infection.

Keywords: ACEIs/ARBs; COVID-19; RAAS; SARS coronavirus (CoV)-2; angiotensin-converting enzyme 2 (ACE2); cardiovascular system; pandemic.

Figure 1

The figure summarizes SARS‐CoV, and presumably SARS‐CoV‐2, confirmed and hypothesized mechanism of viral binding, internalization and shedding via ACE2 interaction, and the successive downregulative effect on ACE2 and the resulting pathogenic effect on lung and cardiac tissues. Abbreviations: angiotensin‐converting enzyme 2 (ACE2); angiotensin (Ang); angiotensin 1‐7 (Ang 1‐7); transmembrane protease, serine 2 (TMPRSS2); ADAM metallopeptidase domain 17 (ADAM‐17); tumour necrosis factor‐α converting enzyme (TACE); SMAD family member2, 7 (SMAD2, SMAD7); nonstructural protein 1 (nsp‐1); SARS‐CoV nucleocapsid (N) protein (N protein); interleukin‐2, 7, 10 (IL‐2, 7,10); granulocyte colony‐stimulating factor (G‐CSF); transforming growth factor‐α (TNF‐α); monocyte chemoattractant protein 1 (MCP‐1).

Figure 2

ACEIs/ARBs effects in cardiovascular disease. Abbreviations: heart failure (HF); left ventricular systolic disfunction (LVSD); acute myocardial infarction (AMI); ST‐segment elevation myocardial infarction (STEMI); non‐ST‐segment elevation myocardial infarction (NSTEMI); diabetes mellitus (DM); ACE inhibitors (ACEIs), myocardial infarction (MI).