Expression of ACE and ACE2 in individuals with diabetic kidney disease and healthy controls.
BACKGROUND
Angiotensin-converting enzyme (ACE) 2 (ACE2) is expressed mainly in the heart and kidney and forms angiotensin-1-7 from angiotensin II. ACE2 might act in a counterregulatory manner to ACE. There is little information about renal ACE and ACE2 expression in human diabetic nephropathy.


METHODS
Cross-sectional study.


METHODS
Kidney tissue from 20 patients with type 2 diabetes and overt nephropathy and 20 healthy kidney donors.


METHODS
Diabetes status.


METHODS
Renal expression of ACE and ACE2 assessed by means of immunohistochemistry and in situ hybridization. Correlation between ACE and ACE2 expression and levels of various biochemical parameters.


RESULTS
Decreased ACE2 and increased ACE expression in both the tubulointerstitium and glomeruli resulted in a significant (P < 0.001) increase in ACE/ACE2 ratio in patients with diabetes with overt nephropathy compared with controls, although ACE messenger RNA in the tubulointerstitium did not significantly increase. ACE/ACE2 ratio correlated positively with values for mean blood pressure, fasting blood glucose, serum creatinine, proteinuria, and hemoglobin A(1c) and inversely with estimated glomerular filtration rate (P < 0.001).


CONCLUSIONS
Inclusion of small number of human renal biopsy specimens with structural distortion of cortical tissue.


CONCLUSIONS
The high ACE/ACE2 ratio in kidneys of patients with type 2 diabetes with overt nephropathy may contribute to renal injury.
Mizuiri
Sonoo
S
Department of Nephrology, Toho University School of Medicine, Tokyo, Japan. sm210@med.toho-u.ac.jp
Hemmi
Hiromichi
H
Arita
Michitsune
M
Ohashi
Yasushi
Y
Tanaka
Yoshihide
Y
Miyagi
Moriatsu
M
Sakai
Ken
K
Ishikawa
Yukio
Y
Shibuya
Kazutoshi
K
Hase
Hiroki
H
Aikawa
Atsushi
A
D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*
D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2