Angiotensin converting enzyme 2 (ACE2) is localized to the glomerular epithelial cells. Since ACE2 promotes the degradation of angiotensin II, a decrease in ACE2 activity could lead to the development of glomerular injury. We gave a specific ACE2 inhibitor, MLN-4760, for 4 weeks to mice rendered diabetic with streptozotocin. The urinary albumin/creatinine ratio was increased along with expansion of the glomerular matrix in diabetic mice treated with the inhibitor compared to the vehicle-treated mice. Glomerular staining of ACE was increased in the diabetic group and was further significantly increased in the diabetic group treated with MLN-4760. In renal vessels, ACE expression was also increased in the diabetic mice and, again, further increased in those diabetic mice treated with the ACE2 inhibitor. Our study shows that chronic pharmacologic ACE2 inhibition worsens glomerular injury in streptozotocin-induced diabetic mice in association with increased ACE expression.

converting enzyme (ACE)2 is a carboxypeptidase that degrades angiotensin II and other peptides. In the kidney, ACE2 localization within the glomerulus and tubules is cell specific. This study was aimed to investigate the localization of ACE2 within the renal vasculature. We also studied the effect of the administration of a specific angiotensin II type 1 receptor blocker, telmisartan, on ACE2 expression in the renal vasculature. ACE2 and ACE were localized in renal arterioles using confocal microscopy and specific cell markers. Quantitative measurements of ACE2 and ACE mRNA were estimated in kidney arterioles isolated by laser capture microdissection using real-time PCR. In kidney arterioles, ACE was localized in the endothelial layer, whereas ACE2 was localized in the tunica media. In mice treated with telmisartan (2 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) for 2 wk, ACE2 expression was increased by immunostaining, whereas ACE expression was decreased. This was reflected in a decrease in the ACE/ ACE2 ratio compared with vehicle-treated controls (0.53 Ϯ 0.14 vs. 7.59 Ϯ 2.72, P ϭ 0.027, respectively). In kidney arterioles isolated by laser capture microdissection, the ACE/ACE2 mRNA ratio was also decreased compared with control mice (1.21 Ϯ 0.31 vs. 4.63 Ϯ 0.86, P ϭ 0.044, respectively). In conclusion, in kidney arterioles ACE2 is preferentially localized in the tunica media, and its expression is increased after administration of the angiotensin II type 1 receptor blocker, telmisartan. Amplification of ACE2 in the renal vasculature may contribute to the therapeutic action of telmisartan by increasing angiotensin II degradation. kidney vessels; angiotensin-converting enzyme; laser microcapture THE RENIN-ANGIOTENSIN SYSTEM (RAS) plays a key role in the control of cardiovascular and renal function (8,13,30). Activation of the RAS has been widely incriminated in the pathophysiology of renal and cardiovascular diseases such as hypertension, myocardial infarction, and heart failure (21, 25). The RAS system primarily involves two enzymes: renin, which cleaves angiotensinogen to the inactive decapeptide angiotensin (ANG) I, and angiotensin-converting enzyme (ACE), a dipeptidyl carboxypeptidase that hydrolyzes ANG I to the octapeptide ANG II (7, 26). The discovery of angiotensinconverting enzyme (ACE)2, the only known enzymatically active homolog of ACE, has added a new level of complexity to the RAS (6, 9). ACE2 degrades ANG II to ANG-(1-7) and ANG I to ANG-(1-9) (10, 17). The impact of these actions of ACE2 and ACE on ANG II as well as the factors that directly or indirectly influence the activity of these enzymes need to be better defined. An understanding of the regulation of these enzymes is clinically relevant in view of recent studies showing that ACE2 expression is altered in pathological conditions such as diabetes, hypertension, and cardiovascular diseases (5,27,28,31,32,34). The potential therapeutic effect of increased ACE2 activity has been recently recognized (2,15,22,33).ANG II type 1 receptor blockers are widely used as an...

Prevalence of stroke in our RTR population was 7.97%. Cerebral hemorrhage appears to be more prevalent in RTR than in general population. More than that, the cerebral hemorrhage rate we found is higher than that reported elsewhere in RTR. The main predictors of stroke were DN, PVD and age. No patient with interstitial nephropathy suffered stroke. Mortality is high in RTR with stroke.

Our study demonstrates that despite the fact that kidney transplantation from elderly deceased donors is associated with reduced graft and patient survival, their paired counterpart patients remaining on dialysis have a risk of death 2.66 times higher.

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