Abstract 387: Individual Biochemical Characterization of the Renin-Angiotensin-System by RAS-Fingerprinting in Healthy Volunteers Treated with RAS-Blockers

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Marko Poglitsch ◽  
Cornelia Schwager ◽  
Oliver Domenig ◽  
Dunja van Oyen ◽  
Manfred Schuster ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Whole Blood ◽  
Biochemical Characterization ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Patient Specific ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Associated Diseases ◽  
Angiotensin Peptides

The Renin-Angiotensin-System (RAS) is critically involved in the regulation of important physiological functions including blood pressure and fluid balance. It is constituted by multiple enzymes giving rise to a meshwork of effector peptides, which mediate their functions through binding to specific receptor molecules. Therefore, the modification of angiotensin peptide levels represents a common strategy for the treatment of RAS-associated diseases and is frequently achieved by the pharmacologic regulation of enzymes taking part in angiotensin metabolism. We developed a highly sensitive method, which allows the simultaneous absolute quantification of up to 10 different angiotensin peptides in human plasma and whole blood (RAS-Fingerprinting). The measurement of RAS-Fingerprints provides unique insights into the physiology of the human RAS and therefore represents a powerful tool for the patient specific evaluation of this physiologically important peptide hormone system. Beside the precise quantification of angiotensin peptides in plasma and whole blood, RAS-Fingerprints analyze the biochemical hardware of the RAS at a previously unachieved level of detail and accuracy. During the development and validation of our LC-MS/MS based method, comprehensive datasets showing multiple applications for RAS-Fingerprinting have been generated. Investigation of healthy volunteers revealed that a patient specific state of the RAS exists, which is defined by a unique composition of RAS enzyme activities that might have crucial effects on the outcome of RAS targeted therapies in individual patients. RAS-Fingerprinting in healthy volunteers treated with an Angiotensin-Receptor-Blockers, ACE-Inhibitor or Renin-Inhibitor revealed that the human RAS reacts to different drugs in a very dynamic and specific way. Therefore, RAS-Fingerprinting could contribute to the development of innovative therapeutic approaches affecting the RAS. The implementation of RAS-Fingerprinting into clinical studies would substantially enhance our understanding of the human RAS and could lead to the development of personalized treatment schemes in the management of RAS-associated diseases in the near future.

Abstract 291: RAS Fingerprinting: Patient-Specific Evaluation of the Renin-Angiotensin-System in Plasma by LC-MS/MS-Based Multiplex Quantification of Angiotensin Peptides

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Marko Poglitsch ◽  
Cornelia Schwager ◽  
Manfred Schuster ◽  
Hans Loibner
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Renin Angiotensin System ◽  
Patient Specific ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Associated Diseases ◽  
Angiotensin Peptides ◽  
Specific Evaluation

The Renin-Angiotensin-System (RAS) is critically involved in the regulation of important physiological functions including blood pressure and fluid balance. It is constituted by multiple enzymes giving rise to a meshwork of effector peptides, which mediate their functions through binding to specific receptor molecules. Therefore, the modification of angiotensin peptide levels represents a common strategy for the treatment of RAS-associated diseases and is frequently achieved by the pharmacologic regulation of enzymes taking part in angiotensin metabolism. We developed a highly sensitive method, which allows the simultaneous absolute quantification of up to 10 different angiotensin peptides in human plasma and whole blood (RAS-Fingerprinting). Either the measurement of in vivo RAS-Fingerprints (immediate sample stabilization) or heparin derived ex vivo RAS-Fingerprints in plasma or whole blood, provide unique insights into the biochemical constitution of the human RAS and therefore represent powerful tools for the patient specific evaluation of this physiologically important peptide hormone system. During the development and validation of a new LC-MS/MS based method for angiotensin quantification, comprehensive datasets for various applications of RAS-Fingerprinting have been generated. RAS-Fingerprints were measured in blood of healthy volunteers during the treatment with different RAS-blockers, which provided deep insights in the physiology and regulation of the human RAS and revealed surprising differences between individual patients. With the help of RAS-Fingerprinting, we were able to re-draw the picture of the human RAS at a previously unachieved level of detail and accuracy. Due to the availability of new selection criteria for pharmacologic screens, RAS-Fingerprinting could contribute to the development of innovative therapeutic approaches affecting the RAS. The extensive utilization of RAS-Fingerprinting in clinical studies will substantially enhance our understanding of the human RAS and could lead to the development of personalized treatment schemes in the management of RAS-associated diseases in the near future.

scholarly journals The Biochemical Effects of Angiotensin-(1-7) on the Oxidative Stress Metabolism and Their Specific Parameters from the Temporal Lobe

2020 ◽  
Vol 71 (6) ◽  
pp. 307-311
Author(s):  
Sorin Ungurianu ◽  
Constantin Trus ◽  
Roxana-Rosmary Enciu
Keyword(s):  
Oxidative Stress ◽  
Temporal Lobe ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Angiotensin Peptides ◽  
Vascular Area ◽  
Ang Iv ◽  
The One

It is already known from a variety of previous reports that an independent brain renin�angiotensin system (RAS) exists, completely separated from the one in the periphery. This independent brain RAS has all the precursors and the enzymatic structures necessary for the generation of the angiotensin peptides. Thus, in the last few years various groups started focusing on the more central effects of less known angiotensins (e.g in comparison with Angiotensin (Ang) II), namely Ang III, Ang IV, Ang-(1�7) or Ang 5-8. One of these newly emerging angiotensins which has become an increased center of interest in many studies is Ang-(1-7), which is a heptapeptide previously described especially for its opposite effects to Ang II, in the peripheral vascular area, but also described for some opposite central functions vs. Ang II. These aspects are completed with the fact that it was recently suggested that the renin�angiotensin system could modulate the oxidative stress metabolism, and also it seems that the manifestations of Angiotensin-(1-7) on the basal oxidative stress status are contradictory, with a variety of reports describing controversial (e.g. both pro-oxidant and antioxidant actions) effects for this heptapeptide. Our results presented here are confirming a possible antioxidant effect of Ang-(1�7) administration on rat, as shown by the increased levels of antioxidant enzymes from the temporal lobe (superoxide dismutase and glutathione peroxidase) and decreased levels of malondialdehyde, as an important lipid peroxidation parameter.

HFrEF pharmacological treatment: ACEIs and/or ARBs

ESC CardioMed ◽  
2018 ◽  
pp. 1844-1848
Author(s):  
Marc A. Pfeffer
Keyword(s):  
Heart Failure ◽  
Angiotensin Receptor Blockers ◽  
Antihypertensive Agents ◽  
Drug Effects ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Reduced Ejection Fraction

Several classes of inhibitors of the renin–angiotensin system were developed as antihypertensive agents. Following the early observations of favourable haemodynamic effects of angiotensin-converting enzyme inhibitors (ACEIs) in patients with congestive heart failure, a series of major randomized outcome trials demonstrated morbidity and mortality benefits of these agents across the spectrum of patients with heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor blockers (ARBs) were then also shown to have similar benefits with a suggestion of some incremental improvements when used together. However, in the trials that randomized patients to a proven dose of an ACEI plus either placebo or an ARB, the combination of the two inhibitors of the renin–angiotensin system resulted in more adverse drug effects without a meaningful improvement in clinical outcomes. This chapter reviews the fundamental underpinnings for use of either an ACEI or ARB to improve prognosis of patients with HFrEF.

scholarly journals Renin-Angiotensin System in Lung Tumor and Microenvironment Interactions

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1457 ◽  
Author(s):  
Maria Joana Catarata ◽  
Ricardo Ribeiro ◽  
Maria José Oliveira ◽  
Carlos Robalo Cordeiro ◽  
Rui Medeiros
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Adjuvant Therapy ◽  
Lung Tumor ◽  
Renin Angiotensin System ◽  
Clinical Settings ◽  
Biological Processes ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Angiotensin Peptides

The mechanistic involvement of the renin-angiotensin system (RAS) reaches beyond cardiovascular physiopathology. Recent knowledge pinpoints a pleiotropic role for this system, particularly in the lung, and mainly through locally regulated alternative molecules and secondary pathways. Angiotensin peptides play a role in cell proliferation, immunoinflammatory response, hypoxia and angiogenesis, which are critical biological processes in lung cancer. This manuscript reviews the literature supporting a role for the renin-angiotensin system in the lung tumor microenvironment and discusses whether blockade of this pathway in clinical settings may serve as an adjuvant therapy in lung cancer.

Imbalance of the renin–angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target?

Gut ◽  
2019 ◽  
Vol 69 (5) ◽  
pp. 841-851 ◽  
Author(s):  
Mayur Garg ◽  
Simon G Royce ◽  
Chris Tikellis ◽  
Claire Shallue ◽  
Duygu Batu ◽  
...  
Keyword(s):  
Ace Inhibitors ◽  
Intestinal Inflammation ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Dependent Manner ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Disease Outcomes ◽  
Collagen Secretion

ObjectiveWe evaluated the influence of the renin–angiotensin system (RAS) on intestinal inflammation and fibrosis.DesignCultured human colonic myofibroblast proliferation and collagen secretion were assessed following treatment with angiotensin (Ang) II and Ang (1–7), their receptor antagonists candesartan and A779, and the ACE inhibitor captopril. Circulating and intestinal RAS components were evaluated in patients with and without IBD. Disease outcomes in patients with IBD treated with ACE inhibitors and angiotensin receptor blockers (ARBs) were assessed in retrospective studies.ResultsHuman colonic myofibroblast proliferation was reduced by Ang (1–7) in a dose-dependent manner (p<0.05). Ang II marginally but not significantly increased proliferation, an effect reversed by candesartan (p<0.001). Colonic myofibroblast collagen secretion was reduced by Ang (1–7) (p<0.05) and captopril (p<0.001), and was increased by Ang II (p<0.001). Patients with IBD had higher circulating renin (mean 25.4 vs 18.6 mIU/L, p=0.026) and ACE2:ACE ratio (mean 0.92 vs 0.69, p=0.015) than controls without IBD. RAS gene transcripts and peptides were identified in healthy and diseased bowels. Colonic mucosal Masson’s trichrome staining correlated with Ang II (r=0.346, p=0.010) and inversely with ACE2 activity (r=−0.373, p=0.006). Patients with IBD who required surgery (1/37 vs 12/75, p=0.034) and hospitalisation (0/34 vs 8/68, p=0.049) over 2 years were less often treated with ACE inhibitors and ARBs than patients not requiring surgery or hospitalisation.ConclusionsThe RAS mediates fibrosis in human cell cultures, is expressed in the intestine and perturbed in intestinal inflammation, and agents targeting this system are associated with improved disease outcomes.

scholarly journals Coronavirus disease 2019 (COVID-19) and the renin-angiotensin system: A closer look at angiotensin-converting enzyme 2 (ACE2)

2020 ◽  
Vol 57 (5) ◽  
pp. 339-350 ◽  
Author(s):  
Annalise E Zemlin ◽  
Owen J Wiese
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
World Health ◽  
Atypical Pneumonia ◽  
Converting Enzyme ◽  
Wholesale Market ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin

Since the first cases of atypical pneumonia linked to the Huanan Seafood Wholesale Market in Wuhan, China, were described in late December 2019, the global landscape has changed radically. In March 2020, the World Health Organization declared COVID-19 a global pandemic, and at the time of writing this review, just over three million individuals have been infected with more than 200,000 deaths globally. Numerous countries are in ‘lockdown’, social distancing is the new norm, even the most advanced healthcare systems are under pressure, and a global economic recession seems inevitable. A novel coronavirus (SARS-CoV-2) was identified as the aetiological agent. From experience with previous coronavirus epidemics, namely the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in 2004 and 2012 respectively, it was postulated that the angiotensin-converting enzyme-2 (ACE2) receptor is a possible port of cell entry. ACE2 is part of the renin-angiotensin system and is also associated with lung and cardiovascular disorders and inflammation. Recent studies have confirmed that ACE2 is the port of entry for SARS-CoV-2. Male sex, advanced age and a number of associated comorbidities have been identified as risk factors for infection with COVID-19. Many high-risk COVID-19 patients with comorbidities are on ACE inhibitors and angiotensin receptor blockers, and this has sparked debate about whether to continue these treatment regimes. Attention has also shifted to ACE2 being a target for future therapies or vaccines against COVID-19. In this review, we discuss COVID-19 and its complex relationship with ACE2.

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.

Use of Renin-Angiotensin System Antagonists in Patients with Hypertension and COVID-19 Infection: A Rapid Review and Meta-analysis

2020 ◽  
Vol 54 ◽  
Author(s):  
Rowena Natividad S. Flores-Genuino ◽  
Charissa Mia Salud-Gnilo ◽  
Evelyn Osio-Salido
Keyword(s):  
Heart Failure ◽  
Angiotensin Receptor Blockers ◽  
Severe Disease ◽  
Renin Angiotensin System ◽  
Rapid Review ◽  
Insufficient Evidence ◽  
Converting Enzyme Inhibitors ◽  
Cross Sectional ◽  
Angiotensin System ◽  
Renin Angiotensin

KEY FINDINGSAmong patients with confirmed COVID-19 infection and hypertension, there is insufficient evidence that RASantagonists are associated with mortality or severe COVID-19 disease.• There is uncertainty with regards to the safe use of renin-angiotensin system (RAS) antagonists, such asangiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), for COVID-19 patientswith hypertension and other comorbidities (heart failure, chronic kidney disease) because of two possiblecontradictory mechanisms 1) upregulation of ACE2 receptors that may facilitate the virus entry into the lung.and 2) control of unabated angiotensin II levels reducing acute lung injury.• Based on very low-quality retrospective cohort studies, there is insufficient evidence that RAS antagonists areassociated with increased mortality (6 studies) or severe disease (10 studies) among patients with confirmedCOVID-19 infection and hypertension.• There are 36 ongoing studies (21 RCTs, 1 single-arm trial, 4 prospective cohorts, 4 retrospective cohorts, 4 casecontrol, and 2 cross-sectional) on this topic.• The European Society of Cardiology (ESC) Council on Hypertension, the International Society of Hypertension(ISH) and the joint statement by the American College of Cardiology (ACC), American Heart Association (AHA),and Heart Failure Society of America (HFSA) all caution against discontinuing RAS-related treatments inpatients with hypertension who become infected with COVID-19.

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