Abstract 379: Insulin Attenuated Albuminuria by Upregulating Angiotensin Converting Enzyme 2 (ACE2) in Type 1 Diabetic Akita Mice

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Esam Salem ◽  
Hari K Somineni ◽  
Harshita Chodavarapu ◽  
Mariana Morris ◽  
Khalid M Elased
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Urinary Albumin Excretion ◽  
Renin Angiotensin System ◽  
Urinary Albumin ◽  
Converting Enzyme ◽  
Diabetic Kidney ◽  
Angiotensin Converting Enzyme 2 ◽  
Albumin Excretion ◽  
Akita Mice

Diabetic nephropathy (DN) is a microvascular complication of diabetes that is clinically diagnosed by a progressive increase in albuminuria. Alterations within renin angiotensin system balance contribute to the pathogenesis of diabetic kidney disease. Angiotensin converting enzyme 2 (ACE2), a metallocarboxypetidase, has a renoprotective role due to its ability to form Angiotensin (1-7) [Ang-(1-7)] by degrading Angiotensin II (Ang II). Accumulating evidence shows that strict glycemic control attenuates diabetic kidney damage. Therefore, the aim of this study is to test the hypothesis that normalizing hyperglycemia with insulin will reduce albuminuria by increasing ACE2 in Akita diabetic mice. Type 1 diabetic Akita mice (C57BL/6-Ins2Akita/J) and their wild type (WT) littermates were used. Metabolic parameters were monitored weekly. Urine was collected over 24 hours to measure the urinary albumin, total protein and ACE2 activity. Akita mice developed significant hyperglycemia (Akita: 452±6; WT: 118±2 mg/dL), hypoinsulinemia (Akita: 0.5; WT: 1.5 ng/mL) and hypoadiponectinemia (Akita: 3.0; WT: 6.0 μg/mL) compared to WT mice. There was a significant increase in urinary albumin excretion (Akita: 2.1±0.2; WT: 0.2±0.06 mg/day) in Akita mice compared to WT mice. In addition, Akita mice demonstrated a significant decrease in renal (Akita: 3±0.3; WT: 4.1±0.1 pmol/hr/μg protein) and urinary (Akita: 0.2±0.03; WT: 0.7±0.1 pmol/hr/μg protein) ACE2 activity compared to WT mice (P<0.05). Western blot & immunohistochemistry revealed downregulation of renal ACE2 & nephrin protein expression in Akita mice compared to WT mice. Treatment with insulin implants (LinβitR) for 10 weeks significantly decreased hyperglycemia in Akita mice (treated: 135±21; untreated: 452±6 mg/dL). Insulin treatment significantly decreased urinary albumin excretion (treated: 0.18±0.2; untreated: 2.1±0.2 mg/day) and increased urinary ACE2 activity (treated: 1.3±0.3; untreated: 0.2±0.03 pmol/hr/μg protein) in Akita mice. In conclusion, normalizing hyperglycemia in Akita mice with insulin increased ACE2 activity and attenuated albuminuria.

scholarly journals Dual RAS blockade normalizes angiotensin-converting enzyme-2 expression and prevents hypertension and tubular apoptosis in Akita angiotensinogen-transgenic mice

2012 ◽  
Vol 302 (7) ◽  
pp. F840-F852 ◽  
Author(s):  
Chao-Sheng Lo ◽  
Fang Liu ◽  
Yixuan Shi ◽  
Hasna Maachi ◽  
Isabelle Chenier ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Gene And Protein Expression ◽  
Intrarenal Ras ◽  
Renal Proximal Tubular ◽  
The Right

We investigated the effects of dual renin-angiotensin system (RAS) blockade on angiotensin-converting enzyme-2 (Ace2) expression, hypertension, and renal proximal tubular cell (RPTC) apoptosis in type 1 diabetic Akita angiotensinogen (Agt)-transgenic (Tg) mice that specifically overexpress Agt in their RPTCs. Adult (11 wk old) male Akita and Akita Agt-Tg mice were treated with two RAS blockers (ANG II receptor type 1 blocker losartan, 30 mg·kg−1·day−1) and angiotensin-converting enzyme (ACE) inhibitor perindopril (4 mg·kg−1·day−1) in drinking water. Same-age non-Akita littermates and Agt-Tg mice served as controls. Blood pressure, blood glucose, and albuminuria were monitored weekly. The animals were euthanized at age 16 wk. The left kidneys were processed for immunohistochemistry and apoptosis studies. Renal proximal tubules were isolated from the right kidneys to assess gene and protein expression. Urinary ANG II and ANG 1–7 were quantified by ELISA. RAS blockade normalized renal Ace2 expression and urinary ANG 1–7 levels (both of which were low in untreated Akita and Akita Agt-Tg), prevented hypertension, albuminuria, tubulointerstitial fibrosis and tubular apoptosis, and inhibited profibrotic and proapoptotic gene expression in RPTCs of Akita and Akita Agt-Tg mice compared with non-Akita controls. Our results demonstrate the effectiveness of RAS blockade in preventing intrarenal RAS activation, hypertension, and nephropathy progression in diabetes and support the important role of intrarenal Ace2 expression in modulating hypertension and renal injury in diabetes.

Urinary Albumin Excretion and Atherosclerosis in Essential Hypertension

1997 ◽  
Vol 92 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Roberto Pedrinelli ◽  
Klaus Undpaintner ◽  
Giulia Dell'omo ◽  
Vinicio Napoli ◽  
Vitantonio Di Bello ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Angiotensin Converting Enzyme ◽  
Systolic Blood Pressure ◽  
Urinary Albumin Excretion ◽  
Urinary Albumin ◽  
Cardiac Mass ◽  
Converting Enzyme ◽  
Albumin Excretion ◽  
Angiotensin Converting Enzyme Genotype

1. Increased urinary albumin excretion is common in patients with essential hypertension and is at least to some extent correlated with prevailing blood pressure levels. However, the generalized vascular dysfunction present in advanced atherosclerotic disease may independently influence this parameter. 2. To evaluate this possibility, we assessed blood pressure, ultrasonographic carotid thickness, cardiac mass, minimum forearm vascular resistances, metabolic parameters and the angiotensin-converting enzyme genotype in patients with untreated essential hypertension and atherosclerotic peripheral vascular disease (n = 11). The results were compared with similar data obtained in matched groups of patients with uncomplicated hypertension and with normotensive control subjects (n = 11 per group). 3. Urinary albumin excretion was higher in hypertensive patients with atherosclerosis than in those without complications; carotid thickness was higher in atherosclerotic patients and a positive, statistically significant correlation existed between this parameter and urinary albumin excretion. In the same patient group, systolic blood pressure, fasting insulin and triacylglycerol levels were elevated and correlated with urinary albumin levels. However, differences in urinary albumin excretion persisted after taking into account the influence of those parameters by analysis of covariance. The distribution of angiotensin-converting enzyme genotype patterns and values of cardiac mass and minimum forearm vascular resistances did not differ significantly among the experimental groups. 4. The data suggest that vascular status may influence urinary albumin excretion in patients with essential hypertension, while confirming the importance of systolic blood pressure levels as a determinant of the raised urinary albumin excretion.

scholarly journals A trimeric human angiotensin-converting enzyme 2 as an anti-SARS-CoV-2 agent in vitro

2020 ◽  
Author(s):  
Tianshu Xiao ◽  
Jianming Lu ◽  
Jun Zhang ◽  
Rebecca I. Johnson ◽  
Lindsay G.A. McKay ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Negative Regulator ◽  
Peptidase Activity ◽  
Converting Enzyme ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2

AbstractEffective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that forms a dimer and serves as the cellular receptor for SARS-CoV-2. It is also a key negative regulator of the renin-angiotensin system (RAS), conserved in mammals, which modulates vascular functions. We report here the properties of a trimeric ACE2 variant, created by a structure-based approach, with binding affinity of ~60 pM for the spike (S) protein of SARS-CoV-2, while preserving the wildtype peptidase activity as well as the ability to block activation of angiotensin II receptor type 1 in the RAS. Moreover, the engineered ACE2 potently inhibits infection of SARS-CoV-2 in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.

Inhibition of angiotensin-converting enzyme reduces urinary albumin excretion but not regional albumin clearance in experimental diabetes

1993 ◽  
Vol 240 (2-3) ◽  
pp. 207-212 ◽  
Author(s):  
Maya Huijberts ◽  
Bruce Wolffenbuttel ◽  
Francy Crijns ◽  
Arie Nieuwenhuijzen Kruseman ◽  
Marc Bemelmans ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Urinary Albumin Excretion ◽  
Experimental Diabetes ◽  
Urinary Albumin ◽  
Converting Enzyme ◽  
Albumin Excretion ◽  
Albumin Clearance

scholarly journals Effect of Combination Therapy with a Calcium Channel Blocker and an Angiotensin-Converting Enzyme Inhibitor on Renal Hypertrophy and Urinary Albumin Excretion in Diabetic Rats

2003 ◽  
Vol 4 (3) ◽  
pp. 191-199 ◽  
Author(s):  
Birgitte Nielsen ◽  
Henning Grønbæk ◽  
Ruth Østerby ◽  
Allan Flyvbjerg
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Urinary Albumin Excretion ◽  
Placebo Treatment ◽  
Diabetic Rats ◽  
Urinary Albumin ◽  
Converting Enzyme ◽  
Albumin Excretion

The objective of this study was to compare the effect of an angiotensin-converting enzyme (ACE) inhibitor and a calcium channel blocker on the development of renal changes in diabetic rats. Diabetes was induced by an intravenous injection of streptozotocin in normotensive Wistar rats. Treatment was commenced immediately in 1 set of rats with 4 treatment arms: nitrendipine (250 mg/kg fodder), enalapril (35 mg/L drinking water), both treatments in combination, or placebo. Treatment was continued for 9 weeks. Another set of rats was left with untreated diabetes for 3 months followed by 7 weeks treatment as above. When starting treatment right after induction of diabetes, nitrendipine significantly reduced urinary albumin excretion (UAE) to the nondiabetic level (P< .05) without reducing blood pressure (BP), whereas enalapril failed to significantly reduce UAE despite a reduction in BP. Combining the two treatments showed no further reduction in UAE compared to monotherapy with nitrendipine, despite a lower BP. When leaving diabetic rats untreated for 3 months, only the coadministration of nitrendipine and enalapril showed a significant reduction in UAE compared to monotherapy and placebo treatment, but showed no significant effect on BP.

scholarly journals Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Target Cells ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Novel Coronavirus

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

scholarly journals Effect of Pentoxifylline on Renal Function and Urinary Albumin Excretion in Patients with Diabetic Kidney Disease: The PREDIAN Trial

2014 ◽  
Vol 26 (1) ◽  
pp. 220-229 ◽  
Author(s):  
Juan F. Navarro-González ◽  
Carmen Mora-Fernández ◽  
Mercedes Muros de Fuentes ◽  
Jesús Chahin ◽  
María L. Méndez ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Urinary Albumin Excretion ◽  
Urinary Albumin ◽  
Diabetic Kidney ◽  
Albumin Excretion
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