The role of angiotensin-converting enzyme 2
Angiotensin-converting enzyme 2 (ACE2) converts angiotensin I (Ang I)
and angiotensin II (Ang II) into the biologically active peptide
Ang-(1-9) and Ang-(1-7), respectively.10,11This
provides counter-regulatory effects of ACE in the
renin-angiotensin-aldosterone system (RAAS). ACE2 could be a functional
receptor and cellular entry point for SARS-CoV-2 and SARS-CoV to invade
target cells in heart, lung, and kidney where prominent expressions of
ACE2 are observed.12,13Although the current evidence
remains insufficient, SARS-CoV-2 might cause direct injury of myocardium
by binding to ACE2.14 Previous data from SARS-CoV
might provide some theoretical mechanism for COVID-19 because SARS-CoV
and SARS-CoV-2 have similar affinity to ACE2.12,13 The
downregulation of myocardial ACE2 expressions after SARS-CoV infection
leads to excessive accumulation of Ang II and causes myocardial injury,
remodeling and even adverse cardiac outcomes.15 This
might underlie AF arrhythmogenesis in COVID-19. Atrial ACE2 expressions
would decrease the levels of transforming growth factor-β1(TGF-β1) and
collagen deposition.16ACE2 might be able to regulate
cardiac action potential.17Laboratory data also
demonstrated that ACE2 metabolites, Ang-(1-7), could modulate
electrophysiological characteristics and calcium hemostasis in atrial
tissue and pulmonary vein cardiomyocytes.18,19The
downregulation of ACE2 in COVID-19 might increase AF vulnerability and
its perpetuation.