Expression of ACE and ACE2 in Individuals With Diabetic Kidney Disease and Healthy Controls

Mizuiri, Sonoo; Hemmi, Hiromichi; Arita, Michitsune; Ohashi, Yasushi; Tanaka, Yoshihide; Miyagi, Moriatsu; Sakai, Ken; Ishikawa, Yukio; Shibuya, Kazutoshi; Hase, Hiroki; Aikawa, Atsushi

doi:10.1053/j.ajkd.2007.11.022

« Previous Next »American Journal of Kidney Diseases
Volume 51, Issue 4 , Pages 613-623, April 2008

Expression of ACE and ACE2 in Individuals With Diabetic Kidney Disease and Healthy Controls

Sonoo Mizuiri, MD
- Department of Nephrology, Toho University School of Medicine, Tokyo, Japan
- Address correspondence to Sonoo Mizuiri, MD, Department of Nephrology, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ohta-ku, Tokyo, 143-8541, Japan.
Hiromichi Hemmi, PhD
- Department of Molecular Biology, Toho University School of Medicine, Tokyo, Japan
Michitsune Arita, PhD
- Department of Molecular Biology, Toho University School of Medicine, Tokyo, Japan
Yasushi Ohashi, MD
- Department of Nephrology, Toho University School of Medicine, Tokyo, Japan
Yoshihide Tanaka, MD
- Department of Nephrology, Toho University School of Medicine, Tokyo, Japan
Moriatsu Miyagi, MD
- Department of Nephrology, Toho University School of Medicine, Tokyo, Japan
Ken Sakai, MD
- Department of Nephrology, Toho University School of Medicine, Tokyo, Japan
Yukio Ishikawa, MD
- Department of Pathology, Toho University School of Medicine, Tokyo, Japan
Kazutoshi Shibuya, MD
- Department of Surgical Pathology, Toho University School of Medicine, Tokyo, Japan
Hiroki Hase, MD
- Division of Nephrology of Ohashi Hospital, Toho University School of Medicine, Tokyo, Japan.
Atsushi Aikawa, MD
- Department of Nephrology, Toho University School of Medicine, Tokyo, Japan

Received 13 May 2007; accepted 19 November 2007. published online 21 February 2008.

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.

Study Design

Cross-sectional study.

Setting & Participants

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

Predictor

Diabetes status.

Outcomes & Measurements

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).