Distinct Regulation of U-ACE2 and P-ACE2 (Urinary and Plasma Angiotensin-Converting Enzyme 2) in a Japanese General Population

Abstract

Severe acute respiratory syndrome coronavirus 2 in coronavirus disease 2019 invades the host through ACE (angiotensin-converting enzyme) 2 as the host cellular receptor for a viral spike protein. ACE2 converts angiotensin II to angiotensin-(1–7) and cleaved ACE2 is detectable in urine and plasma. However, regulation of U-ACE2 (urinary ACE2) and P-ACE2 (plasma ACE2) and their alterations by renin-angiotensin-aldosterone system inhibitors remain unclear. We simultaneously investigated U-ACE2 and P-ACE2 in 605 Japanese participants (male/female: 280/325, mean age: 65±15 years) in the Tanno-Sobetsu cohort study in 2017. Males had significantly lower U-ACE2 and higher P-ACE2 than did females. There was no significant correlation between U-ACE2 and P-ACE2. P-ACE2 was significantly lower in subjects treated with renin-angiotensin-aldosterone system inhibitors than in those not treated with renin-angiotensin-aldosterone system inhibitors, but there was no significant difference in U-ACE2 between the groups. Multivariable regression analyses showed that female sex, high levels of systolic blood pressure, hemoglobin A1c, and urinary albumin-to-creatinine ratio, and low uric acid level were independent predictors of high U-ACE2 level and that high levels of γ-glutamyl transpeptidase, estimated glomerular filtration rate, and uric acid were independent predictors of high P-ACE2 level. In conclusion, U-ACE2 and P-ACE2 are distinctly regulated and the use of renin-angiotensin-aldosterone system inhibitors is not an independent predictor of their levels in a Japanese general population. U-ACE2 is associated with high blood pressure, high glucose level, and microalbuminuria, and low urate level, whereas P-ACE2 is associated with liver dysfunction, high glomerular filtration rate, and high urate level.

Salivary ACE2 and TMPRSS2 link to periodontal status and metabolic parameters

“…Interestingly, we found the consistent sex disparity in salivary levels of soluble ACE2, while there was a marginal but not significant disparity in serum levels of ACE2, in spite of the sex discrepancy in circulating ACE2 levels 55–57,74 . It is postulationally explained by the fact of the high expression of ACE2 in testis, 57 and higher androgen‐regulated TMRPSS2 expression in certain tissues, 72 leading to TMPRSS2‐driven ACE2 shedding 29 .…”

“…Previous studies have revealed the association of increased plasma levels of ACE2 with the risks for the adverse outcomes of CVD 33,61,74,87 . We also examined the relationship of ACE2 and TMPRSS2 with medical parameters.…”

“…The relationship of soluble ACE2 and TMPRSS2 with systemic conditions Previous studies have revealed the association of increased plasma levels of ACE2 with the risks for the adverse outcomes of CVD. 33,61,74,87 We also examined the relationship of ACE2 and TMPRSS2 with medical parameters. Unexpectedly, the present study did not find a significant relationship between ACE2 and TMPRSS2 with medical parameters, possibly due to the limited sample size and exclusion of subjects with systemic diseases.…”

Systematic review and meta-analysis of the clinical outcomes of ACEI/ARB in East-Asian patients with COVID-19

“…In 2017, a human study by Masato et al evaluated the expression of Urinary and Plasma ACE2 receptors in 605 patients who used RAAS system inhibitors. They found the use of RAAS system inhibitors is not an independent predictor of the Urinary and Plasma ACE2 levels, and their levels could also be influenced by other factors like high blood pressure, liver dysfunction and so on [ 45 ]. We know that SARS-CoV-2 enters the human body mainly through the ACE2 receptor of respiratory tract.…”

Angiotensin‐converting enzyme 2 rs2285666 polymorphism and clinical parameters as the determinants of COVID‐19 severity in Iranian population

“…A possible interaction between uric acid and ACE2 could be linked to COVID‐19 getting worse. Additional research on the relationship between ACE2 and uric acid is required in the future (Furuhashi et al., 2021 ; Ishii et al., 2020 ).…”