Study on the Clinical Significance of ACE2 and Its Age-Related Expression

Abstract

Background: ACE2 plays a particular role in the changes in multiple organ functions. However, whether ACE2 expression differs at different ages and whether it plays a role in infection-related organ dysfunction remains unclear.

Methods: Female and male C57BL/6 mice in four different age groups were included in this study. Immunohistochemical and Western blot analyses were performed to evaluate ACE2 expression characteristics in lung tissues. At the same time, we detected the changes of ACE2 in human blood of different ages and evaluated its clinical significance in sepsis-associated organ dysfunction (SAOD).

Results: This study indicated that ACE2 is expressed differently in mouse lung tissues at four different ages (P < 0.05). The peak expression distribution of ACE2 in lung tissues was in the newborn and middle-aged cohorts (P < 0.05). Infants younger than one year had a significantly higher concentration of ACE2 in serum and enhanced susceptibility compared with other ages (P < 0.05). Serum APTT, D-dimer, LDH, and PCT, as well as ACE2 in sepsis and SAOD groups, were statistically significant (P < 0.05) and were related to an increased risk of SAOD. There was a positive correlation between ACE2 and D-dimer (P < 0.05).

Conclusion: The levels of ACE2 expression varied in different age groups. It tends to be higher in infants and young children. This result suggests that young children are more susceptible to infection. Moreover, a cutoff value for the ACE2 level >1551.15 pg/mL and D-dimer >984.5 U/L should be considered a warning sign of infection-associated organ dysfunction and guide the clinician in evaluating the patient's multiple organ function.

Keywords: ACE2; SAOD; clinical significance; infection; organ dysfunction.

Figure 1

ACE2 expression in mouse lung tissues measured via Western blotting: (A) females and (B) males. GAPDH was used as a loading control. Values are represented as mean ± SD (n = 3). The sizes of the molecular weight markers are shown on the right-hand side, representing 130 kDa, 100 kDa, 40 kDa, and 35 kDa proteins. **, P < 0.01.

Figure 2

ACE2 expression in mouse lung tissues by Western blotting: (A) 3-week-old, (B) 8-week-old, (C) 9-month-old. GAPDH was used as a loading control. Values are represented as mean ± SD (n = 4). The sizes of the molecular weight markers are shown on the right-hand side, representing 130 kDa, 100 kDa, 40 kDa, and 35 kDa proteins.

Figure 3

ACE2 expression in mouse lung tissues: as measured via immunohistochemical staining, brownish-yellow indicates the presence of ACE2 expression. Black arrow indicates that ACE2 brown staining deposition is mainly located in bronchial epithelium and alveolar epithelium. (×200).

Figure 4

ACE2 concentration in serum of healthy individuals (pg/mL): (A) comparison of ACE2 among children of different gender (ns P > 0.05) (B) difference of ACE2 in serum of children of different age groups as well as adults (* P < 0.05, **, P < 0.01).

Figure 5

Receiver operating characteristic curve for ACE2 in predicting sepsis-associated organ dysfunction. The area under the curve was 0.800. The best cutoff value for ACE2 was 1551.15 pg/mL (sensitivity: 0.867; specificity: 0.680).

Figure 6

Receiver operating characteristic curve for the D-dimer in predicting sepsis-associated organ dysfunction. The area under the curve was 0.792. The best cutoff value for the D-dimer was 984.5 U/L (sensitivity: 0.692; specificity: 0.875).