4.3 Cardiovascular system impairment in COVID-19
Patients with COVID-19 may have higher risk to develop complications and
progress into severe cases when having coronal heart disease(Huanget al. , 2020). Among the hospitalized patients infected
SARS-CoV-2, acute cardiac injury is one of the common complications. The
cardiac injury found in COVID-19 patients may be at least partially
attributed to the fluctuation of ACE2 expression. Former researches have
proved that elevated cardiac and plasma Ang Ⅱ levels were correlated
with the heart contractility impairment after deletion of ACE2(Gurleyet al. , 2006; Yamamoto et al. , 2006). It was found that
ACE2 has the potential possibility to remodel and regulate heart
function because ACE2 knockout mice has severe cardiac
dysfunction(Nakamura et al. , 2008). Knockout mice of ACE genes or
treatment with AT1 receptor blockers reversed the cardiac phenotype in
ACE2 knockout mice(Oudit et al. , 2007). Similarly, the
age-dependent cardiomyopathy in ACE2 knockout mice is likely mediated by
Ang Ⅱ-induced oxidative stress and inflammation through AT1 receptor by
PI3K signaling. Meanwhile, the correlation between the activity of ACE2
in serum and the deterioration of heart failure has been
confirmed(Goulter et al. , 2004). Especially, in the development
from hypertension to heart failure, the decrease of serum of ACE2
activity suggested a selective biomarker of cardiac systolic
dysfunction(Pan et al. , 2018). Further in vivo murine
studies showed Ang Ⅱ mediated loss of membrane-bound cardiomyocyte ACE2
correlated with the upregulation of TACE/ADAM 17 activity which was
prevented by AT1 receptor blockade(Weber et al. , 1991). Cardiac
fibroblasts and coronary endothelial cells also express ACE2 and TACE
and this reciprocal relationship extends to these cell types as
well(Mehta et al. , 2007). In addition to counterbalancing Ang
Ⅱ/AT1R axis, the involvement of Ang (1-7) in the action of ACE2 on
regulating heart function has been demonstrated. It is reported that the
ACE2/Ang (1-7)/MasR axis plays an importance role in the regulation of
RAAS system(Patel et al. , 2016). Treatment with Ang (1-7) peptide
has been shown to improve myocardial performance, cardiac remodeling,
and even survival in rodent heart failure models(Abwainy et al. ,
2016; Santos et al. , 2004). All these evidences have proved that
the ACE2/Ang (1-7)/MasR axis plays a very important role in
cardiovascular system. Consequently, the impairment of cardiac function
in COVID-19 patients is related to the down-regulation of ACE2/Ang
(1-7)/MasR axis, which implicates the rebalance of RAAS in the treatment
of COVID-19 with cardiovascular system impairment.