Angiotensin-converting enzyme 2 in human plasma and lung tissue

Abstract

Purpose

We investigated plasma angiotensin-converting enzyme 2 (ACE2) concentration in a population sample and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue in patients who underwent lung surgery.

Materials and methods

The study participants were recruited from a residential area in the suburb of Shanghai for the plasma ACE2 concentration study (n = 503) and the lung tissue samples were randomly selected from the storage in Ruijin Hospital (80 men and 78 age-matched women).

Results

In analyses adjusted for covariables, men had a significantly higher plasma ACE2 concentration (1.21 vs. 0.98 ng/mL, p = 0.027) and the mean intensity of ACE2 in the lung tissue (55.1 vs. 53.9 a.u., p = 0.037) than women. With age increasing, plasma ACE2 concentration decreased (p = 0.001), while the mean intensity of ACE2 in the lung tissue tended to increase (p = 0.087). Plasma ACE2 concentration was higher in hypertension than normotension, especially treated hypertension (1.23 vs. 0.98 ng/mL, p = 0.029 vs. normotension), with no significant difference between users of RAS inhibitors and other classes of antihypertensive drugs (p = 0.64). There was no significance of the mean intensity of ACE2 in the lung tissue between patients taking and those not taking RAS inhibitors (p = 0.14). Neither plasma ACE2 concentration nor the mean intensity of ACE2 in the lung tissue differed between normoglycemia and diabetes (p ≥ 0.20).

Conclusion

ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics of patients.

Plain language summary

•  What is the context?

•  • The primary physiological function of ACE2 is the degradation of angiotensin I and II to angiotensin 1-9 and 1-7, respectively.

•  • ACE2 was found to behave as a mediator of the severe acute respiratory syndrome coronavirus (SARS) infection.

•  • There is little research on ACE2 in humans, especially in the lung tissue.

•  • In the present report, we investigated plasma ACE2 concentration and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue respectively in two study populations.

•  What is new?

•  • Our study investigated both circulating and tissue ACE2 in human subjects. The main findings were:

•  • In men as well as women, plasma ACE2 concentration was higher in younger than older participants, whereas the mean intensity of ACE2 in the lung tissue increase with age increasing.

•  • Compared with normotension, hypertensive patients had higher plasma ACE2 concentration but similar mean intensity of ACE2 in the lung tissue.

•  • Neither plasma ACE2 concentration nor lung tissue ACE2 expression significantly differed between users of RAS inhibitors and other classes of antihypertensive drugs.

•  What is the impact?

•  • ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics, such as sex, age, and treated and untreated hypertension.

•  • A major implication is that plasma ACE2 concentration might not be an appropriate surrogate for the ACE2 expression in the lung tissue, and hence not a good predictor of SARS-COV-2 infection or fatality.

Keywords:

• ACE2
• plasma
• lung
• tissue
• hypertension

Acknowledgements

The authors gratefully acknowledge the voluntary participation of all study subjects, the technical assistance of the physicians and nurses of Zhaoxiang Community Health Centre (Qingpu District, Shanghai) and the expert assistance of Jie Wang and Wei-Zhong Zhang (The Shanghai Institute of Hypertension, China). The authors also appreciate the TissueGnostics Asia Pacific Limited for their technical support and the help of Du Yue, the technical engineer.

Disclosures

None.

Conflict of interests

none.

Additional information

Funding

The present study was financially supported by grants from the National Natural Science Foundation of China (grants 82070435, 82070432, 81970353, 81770455, 81770418, 81470533, 81400312, and 91639203), the Ministry of Science and Technology (grant 2016YFC0900902, 2016YFC1300100 and 2018YFC1704902), Beijing, China, and by the Shanghai Commissions of Science and Technology (grant 20411950600, a special grant for COVID-19, and grants 19ZR1443300, 14ZR1436200 and 15XD1503200), and the Shanghai Municipal Health Commission (15GWZK0802, 2017BR025, 201940297, GWV-10.1-XK05 and a Grant for Leading Academics).