Details

Autor(en) / Beteiligte

• Wong, Denise W
• Oudit, Gavin Y
• Reich, Heather
• Kassiri, Zamaneh
• Zhou, Joyce
• Liu, Qiao C
• Backx, Peter H
• Penninger, Josef M
• Herzenberg, Andrew M
• Scholey, James W

Titel

Loss of Angiotensin-Converting Enzyme-2 ( Ace2 ) Accelerates Diabetic Kidney Injury

Ist Teil von

• The American journal of pathology, 2007-08, Vol.171 (2), p.438-451

Ort / Verlag

Bethesda, MD: Elsevier Inc

Erscheinungsjahr

2007

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Diabetic nephropathy is one of the most common causes of end-stage renal failure, but the factors responsible for the development of diabetic nephropathy have not been fully elucidated. We examined the effect of deletion of the angiotensin-converting enzyme 2 ( Ace2 ) gene on diabetic kidney injury. Ace2−/− mice were crossed with Akita mice ( Ins2WT/C96Y ), a model of type 1 diabetes mellitus, and four groups of mice were studied at 3 months of age: Ace2+/y Ins2WT/WT , Ace2−/y Ins2WT/WT , Ace2+/y Ins2WT/C96Y , and Ace2−/y Ins2WT/C96Y. Ace2−/y Ins2WT/C96Y mice exhibited a twofold increase in the urinary albumin excretion rate compared with Ace2+/y Ins2WT/C96Y mice despite similar blood glucose levels. Ace2−/y Ins2WT/C96Y mice were the only group to exhibit increased mesangial matrix scores and glomerular basement membrane thicknesses compared with Ace2+/y Ins2WT/WT mice, accompanied by increased fibronectin and α-smooth muscle actin immunostaining in the glomeruli of Ace2−/y Ins2WT/C96Y mice. There were no differences in blood pressure or heart function to account for the exacerbation of kidney injury. Although kidney levels of angiotensin (Ang) II were not increased in the diabetic mice, treatment with an Ang II receptor blocker reduced urinary albumin excretion rate in Ace2−/y Ins2WT/C96Y mice, suggesting that acceleration of kidney injury in these mice is Ang II-mediated. We conclude that ACE2 plays a protective role in the diabetic kidney, and ACE2 is an important determinant of diabetic nephropathy.