Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle.

Area of Science:

• Physiology
• Molecular Biology
• Exercise Science

Background:

• Skeletal muscle angiotensin-converting enzyme 2 (ACE2) plays a role in cardiovascular regulation and is the receptor for SARS-CoV-2.
• Understanding ACE2 expression in skeletal muscle is crucial for assessing its physiological roles and potential implications in disease.
• Previous research has not fully elucidated the factors influencing ACE2 protein levels in human skeletal muscle, particularly concerning sex differences and fitness levels.

Purpose of the Study:

• To determine sex-based differences in skeletal muscle ACE2 protein expression.
• To investigate the association between ACE2 expression in skeletal muscle and cardiorespiratory fitness (VO2 max) and adiposity (body fat percentage).
• To identify key predictors of ACE2 protein variability in human skeletal muscle.

Main Methods:

• Analysis of vastus lateralis muscle biopsies from 170 men and 69 women using western blot for ACE2 protein expression.
• Measurement of cardiorespiratory fitness (VO2 max) via ergospirometry.
• Assessment of body composition using dual-energy X-ray absorptiometry (DXA) to determine body fat percentage and lean mass.

Main Results:

• Skeletal muscle ACE2 protein expression was 1.8-fold higher in women compared to men (p=0.001).
• This sex difference in ACE2 expression was no longer significant after adjusting for body fat percentage, leg lean mass-adjusted VO2 max (VO2 max-LLM), and age.
• Body fat percentage was the primary predictor of ACE2 expression variability (explaining 5.2% of the variance), with VO2 max-LLM also showing predictive value. A significant interaction between fat percentage and VO2 max-LLM was observed.

Conclusions:

• Women exhibit higher ACE2 protein levels in skeletal muscle than men, a finding largely explained by differences in body fat and cardiorespiratory fitness.
• Body fat percentage is the most significant determinant of ACE2 protein expression variability in human skeletal muscle.
• Cardiorespiratory fitness, particularly when adjusted for lean mass, also influences ACE2 expression, with an interaction effect observed with body fat percentage.