Abstract
The study aimed to determine the levels of skeletal muscle angiotensin‐converting enzyme 2 (ACE2, the SARS‐CoV‐2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age: 19–65 years, weight: 56–137 kg, BMI: 23–44) and 69 women (age: 18–55 years, weight: 41–126 kg, BMI: 22–39) was analyzed in duplicate by western blot. VO2max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8‐fold higher in women than men (p = 0.001, n = 239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2max per kg of legs lean mass (VO2max‐LLM) and age (p = 0.47). Multiple regression analysis showed that the fat % (β = 0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2% of the variance. VO2max‐LLM had also predictive value (β = 0.09). There was a significant fat % by VO2max‐LLM interaction, such that for subjects with low fat %, VO2max‐LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2max‐LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.
Highlights
angiotensin-converting enzyme 2 (ACE2) mRNA overexpression has been reported in patients with comorbidities who are at higher risk of a more severe COVID-1 9.5,6 Male sex, ageing, and low cardiorespiratory fitness and physical inactivity have been associated with increased severity and mortality from COVID-1 9.7–12 it remains unknown whether sex, age, cardiorespiratory fitness, and body composition are associated with different levels of
The ACE2 protein expression levels in skeletal muscle have been determined for the first time in a large sample of men and women, covering a wide range of adiposity, cardiorespiratory fitness, and age
We have shown that premenopausal women express larger amounts of ACE2 protein than men of similar age
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ) penetrates human cells by binding to the angiotensin-converting enzyme 2 (ACE2).[1,2] A high level of ACE2 protein expression may facilitate cell infection and vice versa,[1] and tissue differences in ACE2 expression could explain part of the pathophysiology of the disease.[3,4] ACE2 mRNA overexpression has been reported in patients with comorbidities (hypertension, diabetes, obesity, ischemic cardiomyopathy, among others) who are at higher risk of a more severe COVID-1 9.5,6 Male sex, ageing, and low cardiorespiratory fitness and physical inactivity have been associated with increased severity and mortality from COVID-1 9.7–12 it remains unknown whether sex, age, cardiorespiratory fitness, and body composition are associated with different levels of ACE2 protein expression in humans.ACE2 mRNA is ubiquitously expressed in human tissues and especially abundant in the lungs and testis, and a little less abundant in the kidney, heart, digestive tract and skeletal muscle.13–16 ACE2 is necessary to counteract the canonical renin-a ngiotensin system (RAS).[17].
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