scholarly journals Biologia Futura: is ADAM 17 the reason for COVID-19 susceptibility in hyperglycemic and diabetic patients?

2021 ◽  
Author(s):  
Ganna Stepanova
Keyword(s):  
Glycemic Control ◽  
Viral Entry ◽  
Combined Therapy ◽  
Renin Angiotensin System ◽  
Antioxidant Response ◽  
Diabetic Patients ◽  
Angiotensin System ◽  
Point Of Entry ◽  
Current Controversy ◽  
Ras Blockers

AbstractCOVID-19 is a disease-causing current pandemic. It prevails in patients with pre-existing conditions such as diabetes and hypertension. Renin–angiotensin system was identified as a center of COVID-19 pathophysiology. There is a current controversy concerning the usage of ACE inhibitors and AR blockers in patients with COVID-19. Multiple clinical trials are on the way to determine the effect of RAS blockers in patients with COVID-19. ACE2 receptor is thought to be the point of entry utilized by a coronavirus. However, other factors have been identified which potentially facilitate SARS-CoV-2 entry into the cell. ADAM17 could facilitate viral entry in hyperglycemic and diabetic patients. Insulin is an ADAM17 inhibitor. Heme oxygenase (HO)-1 level is reduced in diabetic patients, contributing to the worst outcome for patients with poor glycemic control. The combined therapy of glycemic control and antioxidant response to oxidative stress could be explored in patients with COVID-19.

scholarly journals ACE2 Shedding and the Role in COVID-19

2022 ◽  
Vol 11 ◽  
Author(s):  
Jieqiong Wang ◽  
Huiying Zhao ◽  
Youzhong An
Keyword(s):  
Amino Acids ◽  
Viral Entry ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Underlying Mechanism ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Transmembrane Glycoprotein

Angiotensin converting enzyme 2 (ACE2), a transmembrane glycoprotein, is an important part of the renin-angiotensin system (RAS). In the COVID-19 epidemic, it was found to be the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). ACE2 maintains homeostasis by inhibiting the Ang II-AT1R axis and activating the Ang I (1-7)-MasR axis, protecting against lung, heart and kidney injury. In addition, ACE2 helps transport amino acids across the membrane. ACE2 sheds from the membrane, producing soluble ACE2 (sACE2). Previous studies have pointed out that sACE2 plays a role in the pathology of the disease, but the underlying mechanism is not yet clear. Recent studies have confirmed that sACE2 can also act as the receptor of SARS-COV-2, mediating viral entry into the cell and then spreading to the infective area. Elevated concentrations of sACE2 are more related to disease. Recombinant human ACE2, an exogenous soluble ACE2, can be used to supplement endogenous ACE2. It may represent a potent COVID-19 treatment in the future. However, the specific administration concentration needs to be further investigated.

scholarly journals Effect of Dual Blockade of Renin-Angiotensin System on Proteinuria

2013 ◽  
Vol 1 (1) ◽  
pp. 18-20
Author(s):  
Eqerem Hasani ◽  
Alma Idrizi ◽  
Myftar Barbullushi
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blocker ◽  
Enzyme Inhibitor ◽  
Combined Therapy ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Dual Blockade

Aim: Aim of the study was the evaluation of the effect of dual blockade of the renin-angiotensin system (RAS) on proteinuria. Material and Methods: Sixty patients, included in the study, were treated with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker for a period of 3 months. Results: The dual blockade of RAS resulted with decrease of proteinuria, a slight increase of serum creatinine and was not associated with a lowering of blood pressure.Conclusion: Combined therapy with ACE-I and ARB results in a more complete blockade of the RAS than monotherapy. In proteinuric nephropathies it reduces significantly baseline proteinuria.

COVID-19 and diabetes mellitus: potential metabolic associations

2021 ◽  
Vol 21 ◽  
Author(s):  
Pedro Henrique Abreu da Silva ◽  
Andressa Santos Garcia ◽  
Fábio Aguiar Alves ◽  
André Luis Souza dos Santos ◽  
Cátia Lacerda Sodré
Keyword(s):  
Diabetes Mellitus ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Renin Angiotensin System ◽  
Cell Receptor ◽  
Protective Role ◽  
Infection Process ◽  
Point Of View ◽  
Diabetic Patients ◽  
Viral Binding

: The COVID-19 pandemic turned the SARS-CoV-2 into the main target of scientific research all around the world. Many advances have already been made, but there is still a long way to go to solve the molecular mechanisms related to the process of the SARS-CoV-2 infection, as well as the particularities of the disease, its course and the complex host-pathogen relationships. However, a lot has been theorized and associated with COVID-19, like the worst prognosis of the disease among individuals with some comorbidities, like diabetes mellitus. In this perspective, diabetic patients are repeatedly associated with more severe cases of COVID-19 when compared to non-diabetic patients. Even though ACE2 (angiotensin-converting enzyme 2) was recognized as the host cell receptor for both binding and entering of SARS-CoV-2 particles, it was also pointed out that this enzyme plays an important protective role against pulmonary damage. Therefore, paradoxically as it may seem, the low baseline level of this receptor in people with diabetes is directly linked to a more expressive loss of ACE2 protective effect, which could be one of the possible factors for the worst prognosis of COVID-19. Still, COVID-19 may also have a diabetogenic effect. From this point of view, the main topics that will be highlighted are (i) the mechanism of the viral entry, with special attention to the cellular receptor (ACE2) and the viral binding protein (spike), (ii) the relationship among the renin-angiotensin system, the infection process and the patients' prognosis, (iii) the glucose control and the medicines used in this event, and (iv) a brief analysis on diabetes triggered by COVID-19.

scholarly journals MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
José María Mora-Gutiérrez ◽  
José Antonio Rodríguez ◽  
María A. Fernández-Seara ◽  
Josune Orbe ◽  
Francisco Javier Escalada ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Early Stage ◽  
Renin Angiotensin System ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Angiotensin System ◽  
Diabetic Kidney ◽  
Renin Angiotensin

AbstractMatrix metalloproteinases have been implicated in diabetic microvascular complications. However, little is known about the pathophysiological links between MMP-10 and the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). We tested the hypothesis that MMP-10 may be up-regulated in early stage DKD, and could be down-regulated by angiotensin II receptor blockade (telmisartan). Serum MMP-10 and TIMP-1 levels were measured in 268 type 2 diabetic subjects and 111 controls. Furthermore, histological and molecular analyses were performed to evaluate the renal expression of Mmp10 and Timp1 in a murine model of early type 2 DKD (db/db) after telmisartan treatment. MMP-10 (473 ± 274 pg/ml vs. 332 ± 151; p = 0.02) and TIMP-1 (573 ± 296 ng/ml vs. 375 ± 317; p < 0.001) levels were significantly increased in diabetic patients as compared to controls. An early increase in MMP-10 and TIMP-1 was observed and a further progressive elevation was found as DKD progressed to end-stage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and significant albuminuria compared to wild-type, which was prevented by telmisartan. MMP-10 and TIMP-1 are increased from the early stages of type 2 diabetes. Prevention of MMP-10 upregulation observed in diabetic mice could be another protective mechanism of RAS blockade in DKD.

scholarly journals Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1367
Author(s):  
Fabrizio Pucci ◽  
Philippe Bogaerts ◽  
Marianne Rooman
Keyword(s):  
Renin Angiotensin System ◽  
Therapeutic Strategies ◽  
Spike Protein ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Pathogenic Mechanisms ◽  
Renin Angiotensin ◽  
Factors Associated ◽  
Ras Blockers ◽  
The Impact

SARS-CoV-2 infection is mediated by the binding of its spike protein to the angiotensin-converting enzyme 2 (ACE2), which plays a pivotal role in the renin-angiotensin system (RAS). The study of RAS dysregulation due to SARS-CoV-2 infection is fundamentally important for a better understanding of the pathogenic mechanisms and risk factors associated with COVID-19 coronavirus disease and to design effective therapeutic strategies. In this context, we developed a mathematical model of RAS based on data regarding protein and peptide concentrations; the model was tested on clinical data from healthy normotensive and hypertensive individuals. We used our model to analyze the impact of SARS-CoV-2 infection on RAS, which we modeled through a downregulation of ACE2 as a function of viral load. We also used it to predict the effect of RAS-targeting drugs, such as RAS-blockers, human recombinant ACE2, and angiotensin 1–7 peptide, on COVID-19 patients; the model predicted an improvement of the clinical outcome for some drugs and a worsening for others. Our model and its predictions constitute a valuable framework for in silico testing of hypotheses about the COVID-19 pathogenic mechanisms and the effect of drugs aiming to restore RAS functionality.

scholarly journals Competing Effects of Renin Angiotensin System Blockade and Sodium-Glucose Cotransporter-2 Inhibitors on Erythropoietin Secretion in Diabetes

2020 ◽  
Vol 51 (5) ◽  
pp. 349-356 ◽  
Author(s):  
Katerina P. Marathias ◽  
Vaia A. Lambadiari ◽  
Konstantinos P. Markakis ◽  
Vassilios D. Vlahakos ◽  
Dimitra Bacharaki ◽  
...  
Keyword(s):  
Angiotensin Receptor Blockers ◽  
Haemoglobin Concentration ◽  
Renin Angiotensin System ◽  
Sglt2 Inhibitors ◽  
Common Finding ◽  
Diabetic Patients ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption

Background: Anaemia is a common finding in diabetes, particularly in those patients with albuminuria or renal dysfunction and is associated with impaired erythropoietin (EPO) secretion. This review focuses on mechanisms involved in the regulation of erythropoiesis in diabetic patients in an effort to elucidate the competing effects of the renin angiotensin system (RAS) blockade and sodium-glucose cotransporter-2 (SGLT2) inhibitors on haemoglobin concentration and hematocrit values. Summary: The RAS shows significant activation in diabetic subjects. Angiotensin II, its active octapeptide, causes renal tubulointerstitial hypoxia, which stimulates hypoxia-inducible factors (HIF) and increases EPO secretion and erythropoiesis. As expected, drugs that inactivate RAS, such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB) are associated with a significant hematocrit-lowering effect and/or anaemia in various clinical conditions, including diabetes. Dual blockade by a combination of ACEi and ARB in diabetic patients achieves a better RAS inhibition, but at the same time a worse drop of haemoglobin concentration. Increased glucose reabsorption by SGLTs in diabetic subjects generates a high-glucose environment in renal tubulointerstitium, which may impair HIF-1, damage renal erythropoietin-producing cells (REPs) and decrease EPO secretion and erythropoiesis. SGLT2 inhibitors, which inhibit glucose reabsorption, may attenuate glucotoxicity in renal tubulointerstitium, allowing REPs to resume their function and increase EPO secretion. Indeed, EPO levels increase within a few weeks after initiation of therapy with all known SGLT2 inhibitors, followed by increased reticulocyte count and a gradual elevation of haemoglobin concentration and hematocrit level, which reach zenith values after 2–3 months. Key Messages: The competing effects of RAS blockade and SGLT2 inhibitors on erythropoiesis may have important clinical implications. The rise of hematocrit values by SGLT2 inhibitors given on top of RAS blockade in recent outcome trials may significantly contribute to the cardiorenal protection attained. The relative contribution of each system to erythropoiesis and outcome remains to be revealed in future studies.

P322Inhibitors of the renin-angiotensin system in diabetic patients with heart failure with preserved ejection fraction treatment: impact of m235t polymorphism of angiotensinogen

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O Medentseva ◽  
I S Rudyk ◽  
M M Udovychenko ◽  
I C Gasanov ◽  
D P Babichev ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Ejection Fraction ◽  
Renin Angiotensin System ◽  
Diabetic Patients ◽  
Preserved Ejection Fraction ◽  
Angiotensin System ◽  
Patients With Heart Failure ◽  
Heart Failure Questionnaire ◽  
M235t Polymorphism

Abstract Background Inhibitors of the renin-angiotensin system plays an important role in chronic heart failure treatment. However, the impact of Angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARBs) on treatment efficacy in diabetic patients with heart failure with preserved preserved ejection fraction (HFpEF) depending on M235T polymorphism of ATG is still unknown. Aim To estimate the efficacy of ACE inhibitors and ARBs therapy in diabetic patient with HFpEF depending on the polymorphism of the M235T of the ATG gene. Methods A total of eighty-two patients (50 females and 32 males; mean age 62,9±8,1 years) with HFpEF and type 2 diabetes mellitus were examined. Sixty-two patients were carriers of 235T allele (MT+TT genotypes), 20 patients had MM genotype of M235T polymorphism of ATG, which was determined by using of polymerase chain reaction. All patients were divided into 4 groups depending on genotypes taking Ramipril or Valsartan during 12 months. Clinical examination, 6 minute walking test, Minnesota Living with Heart Failure Questionnaire (MLHFQ) have been used. All statistical tests were 2-tailed and p<0,05 was considered statistically significant and performed in Statistica 10.0. Results It was not found the significant difference in efficacy of treatment using Valsartan or Ramipril in diabetic patients with genotype MM with HFpEF, whereas in the presence of the T allele of the polymorphism of the M235T ATG, use of valsartan was more effective. Table shows the dynamics of the investigated parameters. Dynamics of parametrs during treatment Parameters HFpEF and DM2T, TT or MT HFpEF and DM2T, MM Ramipril (n=22) Valsartan (n=21) Ramipril (n=10) Valsartan (n=10) Baseline After 12 months treatment Baseline After 12 months treatment Baseline After 12 months treatment Baseline After 12 months treatment SBP, mm Hg 172.0 [157.2; 178.5] 150.0 [132.0; 152.0]* 165.0 [145.3; 174.2] 128.0 [126.0; 134.0]* 167,5 [152.5; 176.0] 140.0 [134.0; 142.0] 160,0 [144.0; 170.0] 146.0 [138.0; 150.0] DBP, mm Hg 98.0 [86.0; 104.0] 92.0 [80.0; 94.0]* 96.0 [82.0; 100.0] 86.0 [80.0; 88.0]* 102.0 [84.0; 106.0] 98.0 [84.0; 100.0] 99.0 [80.0; 100.0] 94.0 [80.0; 96.0] 6 min test, m 313,0 [226,7; 375,5] 320,0 [236,4; 384,6]* 342.5 [258.0; 393.7] 372,0 [262,7; 397,9]* 305.0 [190.5; 375.0] 315.0 [198.5; 384.0] 328.0 [295.0; 401.0] 342.0 [298.0; 410.0] MLHFQ 62,0 [50,0; 71,2] 56,0 [46,5; 68,4]* 61.5 [50.5; 71.5] 40.5 [36.5; 56.5]* 60.0 [47.0; 76.2] 54.0 [43.0; 70.0] 58.0 [49.5; 76.2] 58.0 [49.5; 76.2] Dispnea, % 100 90* 100 70* 100 90 100 80 Edema, % 68,1 54,5* 61,9 33,3* 50 40 60 60 SBP, systolic blood pressure; DBP, diastolic blood pressure; MLHFQ, Minnesota Living with Heart Failure Questionnaire; statistically significant changes (p<0.05). Conclusion Use of Valsartan comparing to Ramipril in diabetic T allele carriers of M235T polymorphism of ATG with HFpEF was independently associated with more effective clinical signs of heart failure improvement, blood pressure decrease, quality of life according to the MLHFQ and physical activity tolerance increase.

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