scholarly journals SARS-CoV-2 Receptor and Renin-Angiotensin System Regulation: Impact of Genetics Variants in ACE2 Gene Impact of Genetics Variants in the ACE2 Gene in the Functional Receptor of SARS-CoV-2

2020 ◽  
Vol 5 (7) ◽  
pp. 489-497
Author(s):  
Juliana de Oliveira Cruz ◽  
Sandra Mara Bispo Sousa
Keyword(s):  
Protein Binding ◽  
Genetic Variants ◽  
Evolutionary Relationship ◽  
Physiological Role ◽  
Renin Angiotensin System ◽  
Spike Protein ◽  
Human Populations ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ace2 Gene

The ACE2 has a physiological role in the regulation of the Renin-Angiotensin System. It is also described your function as a receptor for SARS-CoV-2 and other coronaviruses. Genetic variants in ACE2 are associated with cardiovascular diseases in different human populations and drug response. There is no direct evidence that mutations in ACE2 confer resistance to coronavirus spike protein binding. The evolutionary relationship between spike protein binding and ACE2 is complex. Significant genetic variants are present in ACE2, meanwhile, the evolutionary time of contact of the human ACE2 to the virus is short and, therefore, it did not suffer sufficient selective pressures to offer resistance to viral spike protein binding at the population level. More efforts are needed to identify genetic variants in human ACE2 and other genes, and, consequently, conducting case-control studies to validate these variants and their possible association with infection rates by SARS-CoV-2 and/or clinical outcome.

scholarly journals Interactions between ibuprofen, ACE2, renin‐angiotensin system, and spike protein in the lung. Implications for COVID‐19

2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Rita Valenzuela ◽  
Maria A. Pedrosa ◽  
Pablo Garrido‐Gil ◽  
Carmen M. Labandeira ◽  
Gemma Navarro ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Spike Protein ◽  
Angiotensin System ◽  
Renin Angiotensin

Gene variants of the renin–angiotensin system and hypertension: from a trough of disillusionment to a welcome phase of enlightenment?

2010 ◽  
Vol 118 (8) ◽  
pp. 487-506 ◽  
Author(s):  
Gavin R. Norton ◽  
Richard Brooksbank ◽  
Angela J. Woodiwiss
Keyword(s):  
Association Studies ◽  
Large Population ◽  
Renin Angiotensin System ◽  
Human Populations ◽  
Incomplete Penetrance ◽  
Gene Variants ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Genes ◽  
The Impact

There is substantial evidence to suggest that BP (blood pressure) is an inherited trait. The introduction of gene technologies in the late 1980s generated a sharp phase of over-inflated prospects for polygenic traits such as hypertension. Not unexpectedly, the identification of the responsible loci in human populations has nevertheless proved to be a considerable challenge. Common variants of the RAS (renin–angiotensin system) genes, including of ACE (angiotensin-converting enzyme) and AGT (angiotensinogen) were some of the first shown to be associated with BP. Presently, ACE and AGT are the only gene variants with functional relevance, where linkage studies showing relationships with hypertension have been reproduced in some studies and where large population-based and prospective studies have demonstrated these genes to be predictors of hypertension or BP. Nevertheless, a lack of reproducibility in other linkage and association studies has generated scepticism that only a concerted effort to attempt to explain will rectify. Without these explanations, it is unlikely that this knowledge will translate into the clinical arena. In the present review, we show that many of the previous concerns in the field have been addressed, but we also argue that a considerable amount of careful thought is still required to achieve enlightenment with respect to the role of RAS genes in hypertension. We discuss whether the previously identified problems of poor study design have been completely addressed with regards to the impact of ACE and AGT genes on BP. In the context of RAS genes, we also question whether the significance of ‘incomplete penetrance’ through associated environmental, phenotypic or physiological effects has been duly accounted for; whether appropriate consideration has been given to epistatic interactions between genes; and whether future RAS gene studies should consider variation across the gene by evaluating ‘haplotypes’.

Effect of hypoxia on atrial natriuretic factor and aldosterone regulation in humans

1990 ◽  
Vol 258 (2) ◽  
pp. E243-E248 ◽  
Author(s):  
D. L. Lawrence ◽  
J. B. Skatrud ◽  
Y. Shenker
Keyword(s):  
Atrial Natriuretic Factor ◽  
Acute Hypoxia ◽  
Physiological Role ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Natriuretic Factor ◽  
Hemoglobin Saturation ◽  
Atrial Natriuretic

To evaluate the possible physiological role of atrial natriuretic factor (ANF) on the observed dissociation of aldosterone from the renin-angiotensin system during acute hypoxia, 7 men, ages 18-27 yr, were studied on two separate days for 1 h under hypoxic (12% O2) and normoxic (room air) conditions. Subjects were on a low-salt diet (urinary sodium 67 +/- 13 meq/24 h) and suppressed with dexamethasone. Hemoglobin saturation decreased during hypoxemia to 68 +/- 1% (P less than 0.01), whereas heart rate increased from 65 +/- 3 to 89 +/- 5 beats/min (P less than 0.01). Plasma aldosterone levels decreased 43% from basal during hypoxemia (P less than 0.01), whereas ANF levels increased by 50% (P less than 0.05). Levels of both were unchanged during normoxemia. Plasma renin activity, angiotensin II, blood pressure, and pH did not change under either condition, and plasma cortisol levels were totally suppressed. These results indicate that acute hypoxemia is a potent stimulus for ANF release and that ANF is probably a major factor responsible for the dissociation of aldosterone from the renin-angiotensin system under these conditions.

scholarly journals Genetic variants of the renin-angiotensin system, diabetic nephropathy and hypertension

Diabetologia ◽  
1997 ◽  
Vol 40 (2) ◽  
pp. 193-199 ◽  
Author(s):  
J. Ringel ◽  
J. Beige ◽  
R. Kunz ◽  
A. Distler ◽  
A. M. Sharma
Keyword(s):  
Diabetic Nephropathy ◽  
Genetic Variants ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

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.

Albumin inhibits the insulin-mediated ACE2 increase in cultured podocytes

2014 ◽  
Vol 306 (11) ◽  
pp. F1327-F1334 ◽  
Author(s):  
Eva Márquez ◽  
Marta Riera ◽  
Julio Pascual ◽  
María José Soler
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Real Time ◽  
Real Time Pcr ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Filtration Barrier ◽  
Gene And Protein Expression ◽  
Ace2 Gene

Podocytes are key cells in the glomerular filtration barrier with a major role in the development of diabetic nephropathy. Podocytes are insulin-sensitive cells and have a functionally active local renin-angiotensin system. The presence and activity of angiotensin-converting enzyme 2 (ACE2), the main role of which is cleaving profibrotic and proinflammatory angiotensin-II into angiotensin-(1–7), have been demonstrated in podocytes. Conditionally immortalized mouse podocytes were cultured with insulin in the presence and absence of albumin. We found that insulin increases ACE2 gene and protein expression, by real-time PCR and Western blotting, respectively, and enzymatic activity within the podocyte and these increases were maintained over time. Furthermore, insulin favored an “anti-angiotensin II” regarding ACE/ACE2 gene expression balance and decreased fibronectin gene expression as a marker of fibrosis in the podocytes, all studied by real-time PCR. Similarly, insulin incubation seemed to protect podocytes from cell death, studied by a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. However, all these effects disappeared in the presence of albumin, which may mimic albuminuria, a main feature of DN pathophysiology. Our results suggest that modulation of renin-angiotensin system balance, fibrosis, and apoptosis by insulin in the podocyte may be an important factor in preventing the development and progression of diabetic kidney disease, but the presence of albuminuria seems to block these beneficial effects.

scholarly journals Genetic variants in the renin-angiotensin system genes are associated with cardiovascular-renal-related risk factors in Mexican Americans

2008 ◽  
Vol 124 (5) ◽  
pp. 557-559 ◽  
Author(s):  
Farook Thameem ◽  
V. Saroja Voruganti ◽  
Xin He ◽  
Subrata D. Nath ◽  
John Blangero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Variants ◽  
Mexican Americans ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Related Risk

scholarly journals Impact of genetic variants on the upstream efficacy of renin-angiotensin system inhibitors for the prevention of atrial fibrillation

2016 ◽  
Vol 175 ◽  
pp. 9-17 ◽  
Author(s):  
Jason D. Roberts ◽  
Thomas A. Dewland ◽  
David V. Glidden ◽  
Thomas J. Hoffmann ◽  
Dan E. Arking ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Variants ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin
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