scholarly journals Adeno-Associated Virus Overexpression of Angiotensin-Converting Enzyme-2 Reverses Diabetic Retinopathy in Type 1 Diabetes in Mice

2016 ◽  
Vol 186 (6) ◽  
pp. 1688-1700 ◽  
Author(s):  
James M. Dominguez ◽  
Ping Hu ◽  
Sergio Caballero ◽  
Leni Moldovan ◽  
Amrisha Verma ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Adeno Associated Virus ◽  
Angiotensin Converting Enzyme 2 ◽  
Diabetes In Mice

Urinary ACE2 in healthy adults and patients with uncomplicated type 1 diabetes

2014 ◽  
Vol 92 (8) ◽  
pp. 703-706 ◽  
Author(s):  
David Z.I. Cherney ◽  
Fengxia Xiao ◽  
Joseph Zimpelmann ◽  
Ronnie L.H. Har ◽  
Vesta Lai ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Enzyme Activity ◽  
Angiotensin Converting Enzyme ◽  
Functional Role ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Protein Levels ◽  
Clinical Complications

Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be renoprotective. We determined whether urinary ACE2 enzyme activity and protein levels (ELISA), as well as angiotensinogen and ACE, are elevated during clamped euglycemia (4–6 mmol·L–1) in patients with uncomplicated type 1 diabetes (T1D, n = 58) compared with normoglycemic controls (n = 21). We also measured the effect of clamped hyperglycemia (9–11 mmol·L–1) on each urinary factor in T1D patients. Urinary ACE2 activity and protein levels were higher during clamped euglycemia in T1D compared with the controls (p < 0.0001). In contrast, urinary angiotensinogen levels (p = 0.27) and ACE excretion (p = 0.68) did not differ. In response to clamped hyperglycemia in T1D, urinary ACE2 protein decreased (p < 0.0001), whereas urinary ACE2 activity as well as angiotensinogen and ACE levels remained unchanged. Urinary ACE2 activity and protein expression are increased in T1D patients prior to the onset of clinical complications. Further work is required to determine the functional role of urinary ACE2 in early T1D.

scholarly journals Inhibition of endoplasmic reticulum stress combined with activation of angiotensin-converting enzyme 2: Novel approach for the prevention of endothelial dysfunction in type 1 diabetic rats

2021 ◽  
Author(s):  
Himanshu Sankrityayan ◽  
Ajinath Kale ◽  
Anil Bhanudas Gaikwad
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Type 1 Diabetes ◽  
Endothelial Dysfunction ◽  
Endoplasmic Reticulum Stress ◽  
Angiotensin Converting Enzyme ◽  
Signaling Pathways ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

Persistent hyperglycemia in type 1 diabetes triggers numerous signaling pathways, which may prove deleterious to the endothelium. Since hyperglycemia damages the endothelial layer via multiple signaling pathways, including enhanced oxidative stress, downregulation of angiotensin-converting enzyme2 signaling, and exacerbation of endoplasmic reticulum stress, etc.; hence it becomes difficult to prevent the injury using monotherapy. Thus, the present study was conceived to evaluate the combined effect of endoplasmic reticulum stress inhibition along with angiotensin-converting enzyme-2 activation, two major contributors to hyperglycemia-induced endothelial dysfunction, in preventing endothelial dysfunction associated with type 1 diabetes. Streptozotocin-induced diabetic animals were treated with either diminazene aceturate (5 mg kg-day-1, p.o.) or tauroursodeoxycholic acid, sodium salt (200 mg kg- day-1 i.p.), or both for four weeks. Endothelial dysfunction was evaluated using vasoreactivity assay, where acetylcholine-induced relaxation was assessed in phenylephrine pre-contracted rings. Combination therapy significantly improved vascular relaxation when compared to diabetic control as well as monotherapy. Restoration of nitrite levels along with prevention of collagen led to improved vasodilatation. Moreover, there was an overall reduction in aortic oxidative stress. We conclude that by simultaneously inhibiting ER stress and activating angiotensin-converting enzyme-2 deleterious effects of hyperglycemia on endothelium were significantly alleviated. This could serve as a novel strategy for the prevention of endothelial dysfunction.

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.

scholarly journals Case Report: Isolated hepatosplenic sarcoidosis treatment improving glycaemic control in a type 1 diabetic patient

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 50
Author(s):  
Sérgio Pina ◽  
Teresa Salero ◽  
Mariana Figueiras ◽  
Rui Osório ◽  
Sofia Amálio
Keyword(s):  
Type 1 Diabetes ◽  
Glycaemic Control ◽  
Angiotensin Converting Enzyme ◽  
Ct Scan ◽  
Enzyme Inhibitor ◽  
Systemic Disease ◽  
Insulin Dose ◽  
Beta Thalassemia ◽  
Converting Enzyme

Sarcoidosis is a multi-systemic disease characterized by non-caseating granulomas in various organs. The aetiology is still unknown. Although the liver is the third most commonly affected organ, hepatosplenic sarcoidosis without lung involvement is very uncommon. There is a high frequency of certain autoimmune illnesses observed in sarcoidosis, but association with type 1 diabetes is infrequent. We present the case of a 31-year-old woman, with type 1 diabetes mellitus diagnosed 22 years before with a glycated haemoglobin (HbA1c) above 14%, diabetic nephropathy, retinopathy and neuropathy, hypercholesterolemia and beta thalassemia. She was medicated with an angiotensin-converting enzyme inhibitor, a dihydropyridine calcium antagonist and insulin.   The patient presented with a 4-month history of tiredness, abdominal pain, weight lost and hepatosplenomegaly. Abdominal ultrasound revealed hepatomegaly with regular contours, diffuse heterogeneous texture, containing numerous nodules with slight enlargement of the spleen. Serum angiotensin converting enzyme (ACE) was 67 IU/L and a sedimentation rate of 120 mm/h. Computer tomography (CT) scan confirmed hepatosplenomegaly and suggested infiltration in both organs. Liver biopsies were compatible with sarcoidosis. After ruling other organ involvement, a diagnosis of isolated hepatosplenic sarcoidosis was provided and prednisolone (40mg/day) was started. After a few months the patient developed a corticoid-induced myopathy confirmed with electromyography. Prednisolone was reduced to 20mg/day and azathioprine (50mg/day) treatment initiated. After a 7-month treatment, chest-abdomen-pelvis CT scan showed a marked reduction of the nodularity and hepatosplenomegaly and after 1 year the patient was completely asymptomatic (HbA1c, 7.5%; ACE, 24IU/L). At 18-month follow-up there was no evidence of recurrence (HbA1c, 7%), with optimum glycaemic control with total daily insulin dose lowered to half. This is an uncommon case in which the treatment of hepatosplenic sarcoidosis with regression of sarcoid tissue can help explain the improvement of glycaemic control in this patient.

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.

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