Angiotensin-converting enzyme 2: enhancing the degradation of angiotensin II as a potential therapy for diabetic nephropathy

被引:101
作者
Batlle, Daniel [1 ]
Wysocki, Jan [1 ]
Soler, Maria J. [2 ]
Ranganath, Keerthi [1 ]
机构
[1] Northwestern Univ, Feinberg Sch Med, Div Nephrol & Hypertens, Dept Med, Chicago, IL 60611 USA
[2] Hosp del Mar IMIM, Dept Nephrol, Barcelona, Spain
关键词
angiotensin; diabetic nephropathy; renin-angiotensin system; KIDNEY-DISEASE; GLOMERULAR INJURY; PROXIMAL TUBULES; ACE2; EXPRESSION; TYPE-1; RECEPTOR; SYSTEM; MICE; HOMOLOG; CARBOXYPEPTIDASE; DEFICIENCY;
D O I
10.1038/ki.2011.381
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin II with high efficiency leading to the formation of angiotensin-(1-7). ACE2 within the kidneys is largely localized in tubular epithelial cells and in glomerular epithelial cells. Decreased glomerular expression of this enzyme coupled with increased expression of ACE has been described in diabetic kidney disease, both in mice and humans with type 2 diabetes. Moreover, both ACE2 genetic ablation and pharmacological ACE2 inhibition have been shown to increase albuminuria and promote glomerular injury. Studies using recombinant ACE2 have shown the ability of ACE2 to rapidly metabolize Ang II in vivo and form the basis for future studies to examine the potential of ACE2 amplification in the therapy of diabetic kidney disease and cardiovascular disease. Kidney International (2012) 81, 520-528; doi: 10.1038/ki.2011.381; published online 23 November 2011
引用
收藏
页码:520 / 528
页数:9
相关论文
共 60 条
[51]   Angiotensin-converting enzyme-2: a molecular and cellular perspective [J].
Warner, FJ ;
Smith, AI ;
Hooper, NM ;
Turner, AJ .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2004, 61 (21) :2704-2713
[52]   Loss of angiotensin-converting enzyme-2 (Ace2) accelerates diabetic kidney injury [J].
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. .
AMERICAN JOURNAL OF PATHOLOGY, 2007, 171 (02) :438-451
[53]  
Wysocki J, 2010, J AM SOC NEPHROL, V21, pSA
[54]  
Wysocki J, 2010, J AM SOC NEPHROL, V21, pTH
[55]   ACE and ACE2 activity in diabetic mice [J].
Wysocki, Jan ;
Ye, Minghao ;
Soler, Maria Jose ;
Gurley, Susan B. ;
Xiao, Hong D. ;
Bernstein, Kenneth E. ;
Coffman, Thomas M. ;
Chen, Sheldon ;
Batlle, Daniel .
DIABETES, 2006, 55 (07) :2132-2139
[56]   Targeting the Degradation of Angiotensin II With Recombinant Angiotensin-Converting Enzyme 2 Prevention of Angiotensin II-Dependent Hypertension [J].
Wysocki, Jan ;
Ye, Minghao ;
Rodriguez, Eva ;
Gonzalez-Pacheco, Francisco R. ;
Barrios, Clara ;
Evora, Karla ;
Schuster, Manfred ;
Loibner, Hans ;
Brosnihan, K. Bridget ;
Ferrario, Carlos M. ;
Penninger, Josef M. ;
Batlle, Daniel .
HYPERTENSION, 2010, 55 (01) :90-U160
[57]   Deletion of angiotensin-converting enzyme 2 accelerates pressure overload-induced cardiac dysfunction by increasing local angiotensin II [J].
Yamamoto, K ;
Ohishi, M ;
Katsuya, T ;
Ito, N ;
Ikushima, M ;
Kaibe, M ;
Tatara, Y ;
Shiota, A ;
Sugano, S ;
Takeda, S ;
Rakugi, H ;
Ogihara, T .
HYPERTENSION, 2006, 47 (04) :718-726
[58]   Increased ACE 2 and decreased ACE protein in renal tubules from diabetic mice - A renoprotective combination? [J].
Ye, MH ;
Wysocki, J ;
Naaz, P ;
Salabat, MR ;
LaPointe, MS ;
Batlle, D .
HYPERTENSION, 2004, 43 (05) :1120-1125
[59]   Glomerular localization and expression of angiotensin-converting enzyme 2 and angiotensin-converting enzyme: Implications for albuminuria in diabetes [J].
Ye, Minghao ;
Wysocki, Jan ;
William, Josette ;
Soler, Maria Jose ;
Cokic, Ivan ;
Batlle, Daniel .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 17 (11) :3067-3075
[60]   Collectrin, a collecting duct-specific transmembrane glycoprotein, is a novel homolog of ACE2 and is developmentally regulated in embryonic kidneys [J].
Zhang, H ;
Wada, J ;
Hida, K ;
Tsuchiyama, Y ;
Hiragushi, K ;
Shikata, K ;
Wang, HY ;
Lin, S ;
Kanwar, YS ;
Makino, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (20) :17132-17139