Age- and gender-related difference of ACE2 expression in rat lung

Epidemiologic data suggested that there was an obvious predominance of young adult patients with a slight female proneness in severe acute respiratory syndrome (SARS). The angiotensin-converting enzyme 2 (ACE2) was very recently identified as a functional receptor for SARS virus and is therefore a prime target for pathogenesis and pharmacological intervention. Rats of both genders at three distinct ages (young-adult, 3 months; middle-aged, 12 months; old, 24 months) were evaluated to determine the characteristic of ACE2 expression in lung and the effect of aging and gender on its expression. ACE2 was predominantly expressed in alveolar epithelium, bronchiolar epithelium, endothelium and smooth muscle cells of pulmonary vessels with similar content, whereas no obvious signal was detected in the bronchiolar smooth muscle cells. ACE2 expression is dramatically reduced with aging in both genders: young-adult vs. old P < 0.001 (by 78% in male and 67% in female, respectively) and middle-aged vs. old P < 0.001 (by 71% in male rats and 59% in female rats, respectively). The decrease of ACE2 content was relatively slight between young-adult and middle-aged groups (by 25% in male and 18% in female, respectively). Although there was no gender-related difference of ACE2 in young-adult and middle-aged groups, a significantly higher ACE2 content was detected in old female rats than male. In conclusion, the more elevated ACE2 in young adults as compared to aged groups may contribute to the predominance in SARS attacks in this age group.