269,971 results on '"RENIN-angiotensin system"'
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2. Efficacy and safety of dual renin–angiotensin system (RAS) blockade for non-elderly diabetic kidney disease patients with preserved eGFR
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Mei, Mei, Zeng, Jun, Fang, Li, Xiang, Sha, Sun, Haili, Wen, Chaolin, Chai, Liyin, Chen, Xinqing, Li, Zhuhong, Li, Ning, and Shen, Bingbing
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- 2024
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3. Role of renin angiotensin system inhibitors and metformin in Glioblastoma Therapy: a review.
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Dixon S, O'connor AT, Brooks-Noreiga C, Clark MA, Levy A, and Castejon AM
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- Humans, Animals, Angiotensin-Converting Enzyme Inhibitors pharmacology, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Hypoglycemic Agents therapeutic use, Hypoglycemic Agents pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Metformin therapeutic use, Metformin pharmacology, Glioblastoma drug therapy, Renin-Angiotensin System drug effects, Brain Neoplasms drug therapy
- Abstract
Glioblastoma multiforme (GBM) is a highly aggressive and incurable disease accounting for about 10,000 deaths in the USA each year. Despite the current treatment approach which includes surgery with chemotherapy and radiation therapy, there remains a high prevalence of recurrence. Notable improvements have been observed in persons receiving concurrent antihypertensive drugs such as renin angiotensin inhibitors (RAS) or the antidiabetic drug metformin with standard therapy. Anti-tumoral effects of RAS inhibitors and metformin have been observed in in vitro and in vivo studies. Although clinical trials have shown mixed results, the potential for the use of RAS inhibitors and metformin as adjuvant GBM therapy remains promising. Nevertheless, evidence suggest that these drugs exert multimodal antitumor actions; by particularly targeting several cancer hallmarks. In this review, we highlight the results of clinical studies using multidrug cocktails containing RAS inhibitors and or metformin added to standard therapy for GBM. In addition, we highlight the possible molecular mechanisms by which these repurposed drugs with an excellent safety profile might elicit their anti-tumoral effects. RAS inhibition elicits anti-inflammatory, anti-angiogenic, and immune sensitivity effects in GBM. However, metformin promotes anti-migratory, anti-proliferative and pro-apoptotic effects mainly through the activation of AMP-activated protein kinase. Also, we discussed metformin's potential in targeting both GBM cells as well as GBM associated-stem cells. Finally, we summarize a few drug interactions that may cause an additive or antagonistic effect that may lead to adverse effects and influence treatment outcome., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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4. Dysregulation of the renin-angiotensin system in vascular dementia.
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Tayler HM, Skrobot OA, Baron DH, Kehoe PG, and Miners JS
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- Humans, Male, Female, Aged, Aged, 80 and over, Peptidyl-Dipeptidase A metabolism, Alzheimer Disease metabolism, Alzheimer Disease pathology, White Matter metabolism, White Matter pathology, Middle Aged, Angiotensin-Converting Enzyme 2 metabolism, Brain metabolism, Brain pathology, Dementia, Vascular metabolism, Dementia, Vascular pathology, Renin-Angiotensin System physiology
- Abstract
The renin-angiotensin system (RAS) regulates systemic and cerebral blood flow and is dysregulated in dementia. The major aim of this study was to determine if RAS signalling is dysregulated in vascular dementia. We measured markers of RAS signalling in white matter underlying the frontal and occipital cortex in neuropathologically confirmed cases of vascular dementia (n = 42), Alzheimer's disease (n = 50), mixed AD/VaD (n = 50) and age-matched controls (n = 50). All cases were stratified according to small vessel disease (SVD) severity across both regions. ACE-1 and ACE-2 protein and activity was measured by ELISA and fluorogenic peptide assays respectively, and angiotensin peptide (Ang-II, Ang-III and Ang-(1-7)) levels were measured by ELISA. ACE-1 protein level and enzyme activity, and Ang-II and Ang-III, were elevated in the white matter in vascular dementia in relation to SVD severity. ACE-1 and Ang-II protein levels were inversely related to MAG:PLP1 ratio, a biochemical marker of brain tissue oxygenation that when reduced indicates cerebral hypoperfusion, in a subset of cases. ACE-2 level was elevated in frontal white matter in vascular dementia. Ang-(1-7) level was elevated across all dementia groups compared to age-matched controls but was not related to SVD severity. RAS signalling was not altered in the white matter in Alzheimer's disease. In the overlying frontal cortex, ACE-1 protein was reduced and ACE-2 protein increased in vascular dementia, whereas angiotensin peptide levels were unchanged. These data indicate that RAS signalling is dysregulated in the white matter in vascular dementia and may contribute to the pathogenesis of small vessel disease., (© 2024 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)
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- 2024
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5. Qingda Granule Attenuates Hypertension-Induced Cardiac Damage via Regulating Renin-Angiotensin System Pathway
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Long, Lin-zi, Tan, Ling, Xu, Feng-qin, Yang, Wen-wen, Li, Hong-zheng, Liu, Jian-gang, Wang, Ke, Zhao, Zhi-ru, Wang, Yue-qi, Wang, Chao-ju, Wen, Yi-chao, Huang, Ming-yan, Qu, Hua, Fu, Chang-geng, and Chen, Ke-ji
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- 2024
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6. Renin-angiotensin system inhibitors for patients with mild or moderate chronic kidney disease and heart failure with mildly reduced or preserved ejection fraction.
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Takeuchi S, Kohno T, Goda A, Shiraishi Y, Kitamura M, Nagatomo Y, Takei M, Nomoto M, Soejima K, Kohsaka S, and Yoshikawa T
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- Humans, Male, Female, Aged, Aged, 80 and over, Angiotensin Receptor Antagonists therapeutic use, Middle Aged, Follow-Up Studies, Severity of Illness Index, Renal Insufficiency, Chronic drug therapy, Renal Insufficiency, Chronic physiopathology, Renal Insufficiency, Chronic complications, Stroke Volume physiology, Stroke Volume drug effects, Heart Failure drug therapy, Heart Failure physiopathology, Heart Failure mortality, Renin-Angiotensin System drug effects, Renin-Angiotensin System physiology, Angiotensin-Converting Enzyme Inhibitors therapeutic use
- Abstract
Background: Renin-angiotensin system inhibitors (RASI) reduce adverse cardiovascular events in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤40% and mild or moderate chronic kidney disease (CKD). However, RASI administration rate and its association with long-term outcomes in patients with CKD complicated by HF with LVEF >40% remain unclear., Methods: We analyzed 1923 consecutive patients with LVEF >40% registered within the multicenter database for hospitalized HF. We assessed RASI administration rate and its association with all-cause mortality among patients with mild or moderate CKD (estimated glomerular filtration rate [eGFR]: 30-60 mL/min/1.73 m
2 ). Exploratory subgroups included patients grouped by age (<80, ≥80 years), sex, previous HF hospitalization, B-type natriuretic peptide (higher, lower than median), eGFR (30-44, 45-59 mL/min/1.73 m2 ), systolic blood pressure (<120, ≥120 mmHg), LVEF (41-49, ≥50%), and mineralocorticoid receptor antagonists (MRA) use., Results: Among patients with LVEF >40%, 980 (51.0%) had mild or moderate CKD (age: 81 [74-86] years; male, 52.6%; hypertension, 69.7%; diabetes, 25.9%), and 370 (37.8%) did not receive RASI. RASI use was associated with hypertension, absence of atrial fibrillation, and MRA use. After multivariable adjustments, RASI use was independently associated with lower all-cause mortality over a 2-year median follow-up (hazard ratio: 0.58, 95% confidence interval: 0.43-0.79, P = 0.001), and the mortality rate difference was predominantly due to cardiac death, consistent in all subgroups., Conclusions: Approximately one-third of HF patients with mild or moderate CKD and LVEF >40% were discharged without RASI administration and demonstrated relatively guarded outcomes., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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7. Urinary exosomal mRNAs as biomarkers for predicting the therapeutic effect of renin-angiotensin system inhibitors in IgA nephropathy patients.
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Zhao B, Wang M, Cong Y, Song A, Lu J, Xie K, Dai H, and Gu L
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- Humans, Male, Adult, Female, Middle Aged, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Glomerulonephritis, IGA drug therapy, Glomerulonephritis, IGA urine, Glomerulonephritis, IGA genetics, RNA, Messenger genetics, RNA, Messenger urine, Exosomes genetics, Exosomes metabolism, Biomarkers urine, Renin-Angiotensin System drug effects, Renin-Angiotensin System genetics
- Abstract
Background: Renin-angiotensin system inhibitors (RASi) treatment is the basic therapy for IgA nephropathy (IgAN) patients. However, there is few of biomarker that can predict the efficacy of RASi. This study aimed to find urinary exosomal mRNAs related to the therapeutic effect of RASi in the treatment of proteinuria in IgAN patients., Methods: We divided IgAN patients in screening cohort into A1 (proteinuria increase at 3 months), B1 (proteinuria decrease less than 50 % at 3 months), C1 (proteinuria decrease more than 50 % at 3 months) groups according to changes of proteinuria after treatment. The urinary exosomes were collected before biopsy, RNAs were extracted and analyzed with the microarray assay. The candidate genes were screened by differentially expressed genes (DEGs) analysis and then validated by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort. A receiver operating characteristic (ROC) curve was used to evaluate gene performance in predicting therapeutic effect on RASi reducing proteinuria in IgAN patients., Results: ECE1 and PDE1A mRNAs were significantly different among the three groups, and were gradually decreased among A1, B1 and C1 groups. In the validation cohort, the level of urinary exosomal ECE1 and PDE1A mRNAs were also significantly lower in A2 group compared with C2 group(ECE1, P < 0.001;PDE1A, P < 0.01). Besides, the level of ECE1 mRNA was also lower in B2 group compared with C2 group (P < 0.01). The ROC curve verified that urinary exosomal ECE1 and PDE1A gene level predicted RASi efficacy in IgAN patients with area under curve (AUC) 0.68 and 0.63 respectively., Conclusion: Urinary exosomal ECE1 and PDE1A mRNAs expression can serve as potential biomarkers for predicting the RASi efficacy to reduce proteinuria in IgAN patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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8. Should renin-angiotensin system inhibitors be stopped or not before non-cardiac surgery?
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Halvorsen S, Vranckx P, and van Diepen S
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- Humans, Angiotensin Receptor Antagonists therapeutic use, Angiotensin Receptor Antagonists pharmacology, Surgical Procedures, Operative, Preoperative Care methods, Renin-Angiotensin System drug effects, Renin-Angiotensin System physiology, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Angiotensin-Converting Enzyme Inhibitors pharmacology
- Abstract
Competing Interests: Conflict of interest None declared.
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- 2024
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9. Associations of renin-angiotensin system inhibitor use with brain insulin signaling and neuropathology.
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Tong H, Capuano AW, Mehta RI, Sood A, Bennett DA, Ahima RS, Arnold SE, and Arvanitakis Z
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- Humans, Male, Female, Aged, 80 and over, Aged, Brain metabolism, Brain pathology, Brain drug effects, Proto-Oncogene Proteins c-akt metabolism, Alzheimer Disease metabolism, Alzheimer Disease pathology, Angiotensin Receptor Antagonists pharmacology, Angiotensin-Converting Enzyme Inhibitors pharmacology, Renin-Angiotensin System drug effects, Renin-Angiotensin System physiology, Insulin Receptor Substrate Proteins metabolism, Signal Transduction drug effects, Signal Transduction physiology, Insulin metabolism
- Abstract
Objective: To examine the associations of renin-angiotensin system (RAS) inhibitor use with postmortem brain insulin signaling and neuropathology., Methods: Among Religious Orders Study participants, 150 deceased and autopsied older individuals (75 with diabetes matched to 75 without by age at death, sex, and education) had measurements of insulin receptor substrate-1 (IRS-1) and RAC-alpha serine/threonine protein kinase (AKT1) collected in the prefrontal cortex using ELISA and immunohistochemistry. Alzheimer's disease (AD), brain infarcts, and cerebral vessel pathology data were assessed by systematic neuropathologic evaluations. RAS inhibitor use was determined based on visual inspection of medication containers during study visits. The associations of RAS inhibitor use with brain insulin signaling measures and neuropathology were examined using adjusted regression analyses., Results: Of the 90 RAS inhibitor users (54 with diabetes), 65 had used only angiotensin-converting enzyme inhibitors, 11 only angiotensin II receptor blockers, and 14 used both. RAS inhibitor use was associated with lower pT
308 AKT1/total AKT1, but not with pS307 IRS-1/total IRS-1 or the density of cells stained positive for pS616 IRS-1. RAS inhibitor use was not associated with the level of global AD pathology or amyloid beta burden, but it was associated with a lower tau-neurofibrillary tangle density. Additionally, we found a significant interaction between diabetes and RAS inhibitors on tangle density. Furthermore, AKT1 phosphorylation partially mediated the association of RAS inhibitor use with tau tangle density. Lastly, RAS inhibitor use was associated with more atherosclerosis, but not with other cerebral blood vessel pathologies or cerebral infarcts., Interpretation: Late-life RAS inhibitor use may be associated with lower brain AKT1 phosphorylation and fewer neurofibrillary tangles., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)- Published
- 2024
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10. Dietary supplementation with black cricket (Gryllus assimilis) reverses protein-energy malnutrition and modulates renin-angiotensin system expression in adipose tissue.
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Ribeiro GHM, Guimarães VHD, Teixeira HADS, Farias LC, Guimarães ALS, de Paula AMB, and Santos SHS
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- Animals, Male, Mice, Adiposity, Insulin Resistance, Renin-Angiotensin System drug effects, Dietary Supplements, Gryllidae, Protein-Energy Malnutrition metabolism, Protein-Energy Malnutrition diet therapy, Adipose Tissue metabolism
- Abstract
Edible insects are recognized as promising food sources due to their nutritional composition. Some species, such as Gryllus assimilis, contain proteins, lipids, and carbohydrates of high biological value, which regulate several metabolic functions, including the Renin-Angiotensin System (RAS). In this context, the present study aimed to assess the effects of dietary supplementation with whole Gryllus assimilis powder on the metabolism of malnourished mice. Thirty-two male Swiss mice were used and divided into four treatment groups. The groups were identified as (AIN93-M); AIN93-M + Gryllus assimilis diet (AIN93-M + GA); AIN93-M + Renutrition diet (AIN93-M + REN) and AIN93-M + Renutrition diet + Gryllus assimilis (AIN93-M + REN + GA). The results showed that whole Gryllus assimilis powder inclusion promotes recovery from protein-energy malnutrition, reduces adiposity, and improves glucose tolerance and insulin sensitivity. It also reduces total cholesterol, triglycerides, VLDL, and adipocyte area. We also observed a significant increase in the expression of RAS-related genes, such as ACE2 and MasR, followed by a reduction in Angiotensinogen and ACE. The main findings of the present study suggest the use of black cricket as a viable strategy for the prevention and treatment of protein-energy malnutrition, as well as the reduction of adiposity, and improvement of lipid and glycemic parameters, with antihypertensive potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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11. Does Blocking the Renin-Angiotensin System Mitigate Acute Kidney Injury After Heart Transplantation?
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Goh JHF and Hwang NC
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- Humans, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Postoperative Complications prevention & control, Postoperative Complications etiology, Acute Kidney Injury etiology, Acute Kidney Injury prevention & control, Heart Transplantation adverse effects, Renin-Angiotensin System physiology, Renin-Angiotensin System drug effects
- Abstract
Competing Interests: Declaration of competing interest None.
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- 2024
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12. Impacts of SARS-CoV-2 on brain renin angiotensin system related signaling and its subsequent complications on brain: A theoretical perspective.
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Etebar N, Naderpour S, Akbari S, Zali A, Akhlaghdoust M, Daghighi SM, Baghani M, Sefat F, Hamidi SH, and Rahimzadegan M
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- Humans, Angiotensin-Converting Enzyme 2 metabolism, Animals, Pandemics, Renin-Angiotensin System physiology, COVID-19 metabolism, COVID-19 complications, Brain metabolism, SARS-CoV-2, Signal Transduction physiology
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Cellular ACE2 (cACE2), a vital component of the renin-angiotensin system (RAS), possesses catalytic activity to maintain AngII and Ang 1-7 balance, which is necessary to prevent harmful effects of AngII/AT2R and promote protective pathways of Ang (1-7)/MasR and Ang (1-7)/AT2R. Hemostasis of the brain-RAS is essential for maintaining normal central nervous system (CNS) function. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral disease that causes multi-organ dysfunction. SARS-CoV-2 mainly uses cACE2 to enter the cells and cause its downregulation. This, in turn, prevents the conversion of Ang II to Ang (1-7) and disrupts the normal balance of brain-RAS. Brain-RAS disturbances give rise to one of the pathological pathways in which SARS-CoV-2 suppresses neuroprotective pathways and induces inflammatory cytokines and reactive oxygen species. Finally, these impairments lead to neuroinflammation, neuronal injury, and neurological complications. In conclusion, the influence of RAS on various processes within the brain has significant implications for the neurological manifestations associated with COVID-19. These effects include sensory disturbances, such as olfactory and gustatory dysfunctions, as well as cerebrovascular and brain stem-related disorders, all of which are intertwined with disruptions in the RAS homeostasis of the brain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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13. The effect of glycine on oxidative stress, inflammation and renin-angiotensin system in kidneys and aorta of cyclosporine-administered rats.
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Kalaycı R, Bingül İ, Soluk-Tekkeşin M, Olgaç V, Bekpınar S, and Uysal M
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- Animals, Male, Antioxidants pharmacology, Aorta drug effects, Aorta metabolism, Aorta pathology, Immunosuppressive Agents toxicity, Inflammation chemically induced, Inflammation prevention & control, Rats, Angiotensin II, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents administration & dosage, Receptor, Angiotensin, Type 1 metabolism, Peptidyl-Dipeptidase A metabolism, Oxidative Stress drug effects, Renin-Angiotensin System drug effects, Cyclosporine toxicity, Kidney drug effects, Kidney pathology, Kidney metabolism, NADPH Oxidase 4 metabolism, Glycine pharmacology, Glycine analogs & derivatives, Glycine administration & dosage, Glycine toxicity, Rats, Wistar
- Abstract
Cyclosporine A (CsA) is an immunosuppressive drug, used in organ transplantations. Oxidative stress, inflammation and renin-angiotensin system (RAS) activation play an important role in CsA-toxicity. Glycine (Gly) has antioxidant and anti-inflammatory effects. In this study, Gly was investigated for its protective role against CsA-induced toxicity. CsA (20 mg/kg/day; subcutaneously) was administered to rats along with Gly injection (250 or 1000 mg/kg; intraperitoneally) for 21 days. Renal function markers [serum urea and creatinine and urinary protein and kidney injury molecule levels and creatinine clearance values] together with histopathological examinations were performed. Oxidative stress (reactive oxygen species, thiobarbutiric acid reactive substances, advanced oxidation products of protein, glutathione, ferric reducing anti-oxidant power and 4-hydroxynonenal levels), and inflammation (myeloperoxidase activity) were determined in kidney tissue. The RAS system [angiotensin II (Ang II) levels, and mRNA expressions of angiotensin converting enzyme (ACE), angiotensin II type-I receptor (AT1R)] and NADPH-oxidase 4 (NOX4) were measured in kidney and aorta. CsA caused significant disturbances in renal function markers, increases in oxidative stress and inflammation parameters and renal damage. Serum angiotensin II levels and mRNA expressions of ACE, AT1R and NOX4 elevated in the aorta and kidney of CsA-rats. Gly, especially its high-dose, alleviated renal function markers, oxidative stress, inflammation and renal damage in CsA-rats. Moreover, serum Ang II levels and mRNA expressions of ACE, AT1R and NOX4 decreased significantly in aorta and kidney in CsA-rats due to Gly treatment. Our results indicate that Gly may be useful for the prevention of CsA-induced renal and vascular toxicity.
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- 2024
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14. Renin-angiotensin system-mediated nitric oxide signaling in podocytes.
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Semenikhina M, Bohovyk R, Fedoriuk M, Stefanenko M, Klemens CA, Oates JC, Staruschenko A, and Palygin O
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- Animals, Humans, Cells, Cultured, Angiotensin I metabolism, Rats, Calcium Signaling drug effects, Male, Angiotensin III metabolism, Angiotensin III pharmacology, Peptide Fragments metabolism, Peptide Fragments pharmacology, Podocytes metabolism, Nitric Oxide metabolism, Renin-Angiotensin System physiology, Angiotensin II pharmacology, Receptor, Angiotensin, Type 2 metabolism, Signal Transduction
- Abstract
Nitric oxide (NO) is widely recognized for its role in regulating renal function and blood pressure. However, the precise mechanisms by which NO affects renal epithelial cells remain understudied. Our previous research has shown that NO signaling in glomerular podocytes can be initiated by Angiotensin II (ANG II) but not by ATP. This study aims to elucidate the crucial interplay between the renin-angiotensin system (RAS) and NO production in podocytes. To conduct our research, we used cultured human podocytes and freshly isolated rat glomeruli. A variety of RAS peptides were used, alongside confocal microscopy, to detect NO production and NO/Ca
2+ cross talk. Dynamic changes in the podocyte cytoskeleton, mediated by RAS-NO intracellular signaling, were observed using fluorescent labeling for F-actin and scanning probe microscopy. The experiments demonstrated that ANG II and ANG III generated high levels of NO by activating the angiotensin II type 2 receptor (AT2 R). We did not detect functional MAS receptor presence in podocytes, and the moderate NO response to ANG 1-7 was also mediated through AT2 R. Furthermore, NO production impacted intracellular Ca2+ signaling and correlated with an increase in podocyte volume and growth. Scanning probe experiments revealed that AT2 R activation and the corresponding NO generation are responsible for the protrusion of podocyte lamellipodia. Taken together, our data indicate that AT2 R activation enhances NO production in podocytes and subsequently mediates changes in Ca2+ signaling and podocyte volume dynamics. These mechanisms may play a significant role in both physiological and pathophysiological interactions between the RAS and podocytes. NEW & NOTEWORTHY The renin-angiotensin system plays a crucial role in the production of intracellular nitric oxide within podocytes. This mechanism operates through the activation of the angiotensin II type 2 receptor, leading to dynamic modifications in intracellular calcium levels and the actin filament network. This intricate process is vital for linking the activity of angiotensin receptors to podocyte function.- Published
- 2024
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15. Timing matters in the use of renin-angiotensin system modulators and COVID-related cognitive and cerebrovascular dysfunction.
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Meier M, Becker S, Levine E, DuFresne O, Foster K, Moore J, Burnett FN, Hermanns VC, Heath SP, Abdelsaid M, and Coucha M
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- Animals, Humans, Mice, Male, Female, Aged, Middle Aged, Cerebrovascular Disorders drug therapy, COVID-19 Drug Treatment, Cognition drug effects, COVID-19 complications, Renin-Angiotensin System drug effects, Angiotensin Receptor Antagonists therapeutic use, Angiotensin Receptor Antagonists pharmacology, Cognitive Dysfunction drug therapy, Cognitive Dysfunction etiology, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Angiotensin-Converting Enzyme Inhibitors pharmacology, Angiotensin-Converting Enzyme 2 metabolism, SARS-CoV-2
- Abstract
Renin-angiotensin system (RAS) modulators, including Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI), are effective medications for controlling blood pressure. Cognitive deficits, including lack of concentration, memory loss, and confusion, were reported after COVID-19 infection. ARBs or ACEI increase the expression of angiotensin-converting enzyme-2 (ACE-2), a functional receptor that allows binding of SARS-CoV-2 spike protein for cellular invasion. To date, the association between the use of RAS modulators and the severity of COVID-19 cognitive dysfunction is still controversial., Purpose: This study addressed the following questions: 1) Does prior treatment with RAS modulator worsen COVID-19-induced cerebrovascular and cognitive dysfunction? 2) Can post-treatment with RAS modulator improve cognitive performance and cerebrovascular function following COVID-19? We hypothesize that pre-treatment exacerbates COVID-19-induced detrimental effects while post-treatment displays protective effects., Methods: Clinical study: Patients diagnosed with COVID-19 between May 2020 and December 2022 were identified through the electronic medical record system. Inclusion criteria comprised a documented medical history of hypertension treated with at least one antihypertensive medication. Subsequently, patients were categorized into two groups: those who had been prescribed ACEIs or ARBs before admission and those who had not received such treatment before admission. Each patient was evaluated on admission for signs of neurologic dysfunction. Pre-clinical study: Humanized ACE-2 transgenic knock-in mice received the SARS-CoV-2 spike protein via jugular vein injection for 2 weeks. One group had received Losartan (10 mg/kg), an ARB, in their drinking water for two weeks before the injection, while the other group began Losartan treatment after the spike protein injection. Cognitive functions, cerebral blood flow, and cerebrovascular density were determined in all experimental groups. Moreover, vascular inflammation and cell death were assessed., Results: Signs of neurological dysfunction were observed in 97 out of 177 patients (51%) taking ACEIs/ARBs prior to admission, compared to 32 out of 118 patients (27%) not receiving ACEI or ARBs. In animal studies, spike protein injection increased vascular inflammation, increased endothelial cell apoptosis, and reduced cerebrovascular density. In parallel, spike protein decreased cerebral blood flow and cognitive function. Our results showed that pretreatment with Losartan exacerbated these effects. However, post-treatment with Losartan prevented spike protein-induced vascular and neurological dysfunctions., Conclusion: Our clinical data showed that the use of RAS modulators before encountering COVID-19 can initially exacerbate vascular and neurological dysfunctions. Similar findings were demonstrated in the in-vivo experiments; however, the protective effects of targeting the RAS become apparent in the animal model when the treatment is initiated after spike protein injection., Competing Interests: Some data were presented as an abstract at the International Stroke Conference 2023 and the MIDYEAR 2023 Clinical Meeting & Exhibition. The authors have declared that no competing interests exist. Funding:This study was supported by American Heart Association 23AIREA1045073 to MA., (Copyright: © 2024 Meier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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16. Discontinuation of renin-angiotensin system inhibitors brings no benefits in severe chronic kidney disease.
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Volpe M and Patrono C
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- Humans, Angiotensin Receptor Antagonists therapeutic use, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Renin-Angiotensin System drug effects, Renal Insufficiency, Chronic drug therapy, Renal Insufficiency, Chronic complications
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- 2024
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17. Renin angiotensin system-induced muscle wasting: putative mechanisms and implications for clinicians
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Afsar, Baris, Afsar, Rengin Elsurer, Caliskan, Yasar, Lentine, Krista L., and Edwards, John C.
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- 2024
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18. Effect of exercise duration on toluene-induced locomotor sensitization in mice: a focus on the Renin Angiotensin System
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Gallardo-Ortíz, Itzell A., Oros-González, Alain, Rodríguez-Manzo, Gabriela, Garduño-Gutiérrez, René, Aragón-Martínez, Andrés, and Páez-Martínez, Nayeli
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- 2024
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19. Pyridostigmine attenuates hypertension by inhibiting activation of the renin-angiotensin system in the hypothalamic paraventricular nucleus
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Lu, Yi, Wang, Yi-dong, Xu, Tian-qi, Zhao, Xu-he, Zhou, Jun, Jin, Lian-hai, and Liu, Jin-jun
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- 2024
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20. Association between stopping renin-angiotensin system inhibitors immediately before hemodialysis initiation and subsequent cardiovascular events
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Nakamura, Yoshihiro, Inaguma, Daijo, Imaizumi, Takahiro, Kurasawa, Shimon, Hishida, Manabu, Okazaki, Masaki, Fujishima, Yuki, Nishibori, Nobuhiro, Suzuki, Katsuhiko, Takeda, Yuki, and Maruyama, Shoichi
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- 2024
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21. The potential role of renin angiotensin system in acute leukemia: a narrative review.
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Portes E Silva KR, Nogueira EM, Jesus Mendes AL, Pena ALB, and Simões E Silva AC
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- Humans, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute pathology, Signal Transduction, Angiotensin I metabolism, Neovascularization, Pathologic metabolism, Animals, Peptide Fragments metabolism, Renin-Angiotensin System physiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Angiotensin II metabolism
- Abstract
Acute leukemias (ALs) are the most common cancers in pediatric population. There are two types of ALs: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Some studies suggest that the Renin Angiotensin System (RAS) has a role in ALs. RAS signaling modulates, directly and indirectly, cellular activity in different cancers, affecting tumor cells and angiogenesis. Our review aimed to summarize the role of RAS in ALs and to explore future perspectives for the treatment of these hematological malignancies by modulating RAS molecules. The database including Pubmed, Scopus, Cochrane Library, and Scielo were searched to find articles about RAS molecules in ALL and in pediatric patients. The search terms were "RAS", "Acute Leukemia", "ALL", "Angiotensin-(1-7)", "Pediatric", "Cancer", "Angiotensin II", "AML". In the bone marrow, RAS has been found to play a key role in blood cell formation, affecting several processes including apoptosis, cell proliferation, mobilization, intracellular signaling, angiogenesis, fibrosis, and inflammation. Local tissue RAS modulates tumor growth and metastasis through autocrine and paracrine actions. RAS mainly acts via two molecules, Angiotensin II (Ang II) and Angiotensin (1-7) [Ang-(1-7)]. While Ang II promotes tumor cell growth and stimulates angiogenesis, Ang-(1-7) inhibits the proliferation of neoplastic cells and the angiogenesis, suggesting a potential therapeutic role of this molecule in ALL. The interaction between ALs and RAS reveals a complex network of molecules that can affect the hematopoiesis and the development of hematological cancers. Understanding these interactions could pave the way for innovative therapeutic approaches targeting RAS components., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
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- 2024
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22. The potential role of brain renin-angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat?
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Al-Qahtani Z, Al-Kuraishy HM, Al-Gareeb AI, Albuhadily AK, Ali NH, Alexiou A, Papadakis M, Saad HM, and Batiha GE
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- Humans, Animals, Angiotensin Receptor Antagonists therapeutic use, Angiotensin Receptor Antagonists pharmacology, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Angiotensin-Converting Enzyme Inhibitors pharmacology, Renin-Angiotensin System, Parkinson Disease metabolism, Parkinson Disease pathology, Brain pathology, Brain metabolism
- Abstract
Parkinson disease (PD) is one of the most common neurodegenerative diseases of the brain. Of note, brain renin-angiotensin system (RAS) is intricate in the PD neuropathology through modulation of oxidative stress, mitochondrial dysfunction and neuroinflammation. Therefore, modulation of brain RAS by angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may be effective in reducing the risk and PD neuropathology. It has been shown that all components including the peptides and enzymes of the RAS are present in the different brain areas. Brain RAS plays a critical role in the regulation of memory and cognitive function, and in the controlling of central blood pressure. However, exaggerated brain RAS is implicated in the pathogenesis of different neurodegenerative diseases including PD. Two well-known pathways of brain RAS are recognized including; the classical pathway which is mainly mediated by AngII/AT1R has detrimental effects. Conversely, the non-classical pathway which is mostly mediated by ACE2/Ang1-7/MASR and AngII/AT2R has beneficial effects against PD neuropathology. Exaggerated brain RAS affects the viability of dopaminergic neurons. However, the fundamental mechanism of brain RAS in PD neuropathology was not fully elucidated. Consequently, the purpose of this review is to disclose the mechanistic role of RAS in in the pathogenesis of PD. In addition, we try to revise how the ACEIs and ARBs can be developed for therapeutics in PD., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
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- 2024
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23. Adipose tissue plasticity mediated by the counterregulatory axis of the renin-angiotensin system: Role of Mas and MrgD receptors.
- Author
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Proença AB, Medeiros GR, Reis GDS, Losito LDF, Ferraz LM, Bargut TCL, Soares NP, Alexandre-Santos B, Campagnole-Santos MJ, Magliano DC, Nobrega ACLD, Santos RAS, and Frantz EDC
- Subjects
- Animals, Humans, Adipose Tissue, Brown metabolism, Adipose Tissue, White metabolism, Energy Metabolism, Obesity metabolism, Obesity pathology, Signal Transduction, Adipose Tissue metabolism, Proto-Oncogene Mas, Receptors, G-Protein-Coupled metabolism, Renin-Angiotensin System physiology
- Abstract
The renin-angiotensin system (RAS) is an endocrine system composed of two main axes: the classical and the counterregulatory, very often displaying opposing effects. The classical axis, primarily mediated by angiotensin receptors type 1 (AT1R), is linked to obesity-associated metabolic effects. On the other hand, the counterregulatory axis appears to exert antiobesity effects through the activation of two receptors, the G protein-coupled receptor (MasR) and Mas-related receptor type D (MrgD). The local RAS in adipose organ has prompted extensive research into white adipose tissue and brown adipose tissue (BAT), with a key role in regulating the cellular and metabolic plasticity of these tissues. The MasR activation favors the brown plasticity signature in the adipose organ by improve the thermogenesis, adipogenesis, and lipolysis, decrease the inflammatory state, and overall energy homeostasis. The MrgD metabolic effects are related to the maintenance of BAT functionality, but the signaling remains unexplored. This review provides a summary of RAS counterregulatory actions triggered by Mas and MrgD receptors on adipose tissue plasticity. Focus on the effects related to the morphology and function of adipose tissue, especially from animal studies, will be given targeting new avenues for treatment of obesity-associated metabolic effects., (© 2024 Wiley Periodicals LLC.)
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- 2024
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24. Unraveling the crosstalk between renin-angiotensin system receptors.
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Gironacci MM and Bruna-Haupt E
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- Humans, Animals, Signal Transduction physiology, Receptor Cross-Talk physiology, Receptors, Angiotensin metabolism, Receptor, Angiotensin, Type 1 metabolism, Blood Pressure physiology, Receptor, Angiotensin, Type 2 metabolism, Renin-Angiotensin System physiology, Receptors, G-Protein-Coupled metabolism
- Abstract
The renin-angiotensin system (RAS) plays a key role in blood pressure regulation. The RAS is a complex interconnected system composed of two axes with opposite effects. The pressor arm, represented by angiotensin (Ang) II and the AT
1 receptor (AT1 R), mediates the vasoconstrictor, proliferative, hypertensive, oxidative, and pro-inflammatory effects of the RAS, while the depressor/protective arm, represented by Ang-(1-7), its Mas receptor (MasR) and the AT2 receptor (AT2 R), opposes the actions elicited by the pressor arm. The AT1 R, AT2 R, and MasR belong to the G-protein-coupled receptor (GPCR) family. GPCRs operate not only as monomers, but they can also function in dimeric (homo and hetero) or higher-order oligomeric states. Due to the interaction with other receptors, GPCR properties may change: receptor affinity, trafficking, signaling, and its biological function may be altered. Thus, heteromerization provides a newly recognized means of modulation of receptor function, as well as crosstalk between GPCRs. This review is focused on angiotensin receptors, and how their properties are influenced by crosstalk with other receptors, adding more complexity to an already complex system and potentially opening up new therapeutic approaches., (© 2024 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)- Published
- 2024
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25. Impact of Renin-Angiotensin System Inhibitors Continuation on Outcome After Major Surgery (STOPORNOT)
- Published
- 2024
26. Cardiac Effects of Renin-Angiotensin System Inhibitors in Nonproteinuric CKD.
- Author
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Shulman RS, Yang W, Cohen DL, Reese PP, and Cohen JB
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- Humans, Male, Female, Middle Aged, Aged, Hypertension drug therapy, Hypertension physiopathology, Cardiovascular Diseases mortality, Cardiovascular Diseases drug therapy, Proportional Hazards Models, Adult, Angiotensin Receptor Antagonists therapeutic use, Renal Insufficiency, Chronic drug therapy, Renal Insufficiency, Chronic physiopathology, Renal Insufficiency, Chronic mortality, Renal Insufficiency, Chronic complications, Renin-Angiotensin System drug effects, Antihypertensive Agents therapeutic use, Angiotensin-Converting Enzyme Inhibitors therapeutic use
- Abstract
Background: In contrast to proteinuric chronic kidney disease (CKD), the relative cardioprotective benefits of antihypertensive medications in nonproteinuric CKD are unknown. We examined long-term cardiovascular outcomes and mortality in patients with nonproteinuric CKD treated with renin-angiotensin system inhibitors (RASIs) versus other antihypertensive medications., Methods: Among participants of the CRIC study (Chronic Renal Insufficiency Cohort) without proteinuria, we used intention-to-treat analyses with inverse probability of treatment weighting and Cox proportional hazards modeling to determine the association of RASIs versus other antihypertensive medications with a composite cardiovascular outcome (myocardial infarction, stroke, heart failure hospitalization, and death) and mortality. Secondary analyses included per-protocol analyses accounting for continuous adherence and time-updated analyses accounting for the proportion of time using RASIs during follow-up., Results: A total of 2806 participants met the inclusion criteria. In the intention-to-treat analyses, RASIs versus other antihypertensive medications were not associated with an appreciable difference in cardiovascular events (adjusted hazard ratio [aHR], 0.94 [95% CI, 0.80-1.11]) or mortality (aHR, 1.06 [95% CI, 0.88-1.28]). In the per-protocol analyses, RASIs were associated with a lower risk of adverse cardiovascular events (aHR, 0.78 [95% CI, 0.63-0.97]) and mortality (aHR, 0.64 [95% CI, 0.48-0.85]). Similarly, in the time-updated analyses, a higher proportion of RASI use over time was associated with a lower mortality risk (aHR, 0.33 [95% CI, 0.14-0.86])., Conclusions: Among individuals with nonproteinuric CKD, after accounting for time-updated use, RASIs are associated with fewer cardiovascular events and a lower mortality risk compared with other antihypertensive medications. Patients with nonproteinuric CKD may benefit from prioritizing RASIs for hypertension management., Competing Interests: None.
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- 2024
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27. The epigenetic legacy of renin-angiotensin system inhibition in preventing hypertension.
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Nosalski R and Lemoli M
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- Humans, Animals, Blood Pressure drug effects, Blood Pressure genetics, Genetic Predisposition to Disease, Renin-Angiotensin System genetics, Renin-Angiotensin System drug effects, Hypertension genetics, Hypertension physiopathology, Hypertension metabolism, Epigenesis, Genetic, Antihypertensive Agents therapeutic use, Angiotensin-Converting Enzyme Inhibitors therapeutic use
- Abstract
Competing Interests: Conflict of interest: None declared. This manuscript was handled by Deputy Editor Charalambos Antoniades.
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- 2024
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28. Four-week inhibition of the renin-angiotensin system in spontaneously hypertensive rats results in persistently lower blood pressure with reduced kidney renin and changes in expression of relevant gene networks.
- Author
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Byars SG, Prestes PR, Suphapimol V, Takeuchi F, De Vries N, Maier MC, Melo M, Balding D, Samani N, Allen AM, Kato N, Wilkinson-Berka JL, Charchar F, and Harrap SB
- Subjects
- Animals, Rats, Arterial Pressure drug effects, Blood Pressure drug effects, Blood Pressure genetics, Epigenesis, Genetic drug effects, Gene Expression Regulation, Time Factors, Transcriptome, Angiotensin II Type 1 Receptor Blockers pharmacology, Angiotensin-Converting Enzyme Inhibitors pharmacology, Antihypertensive Agents pharmacology, Disease Models, Animal, DNA Methylation drug effects, Gene Regulatory Networks, Hypertension physiopathology, Hypertension genetics, Hypertension drug therapy, Hypertension metabolism, Kidney metabolism, Kidney drug effects, Losartan pharmacology, Perindopril pharmacology, Rats, Inbred SHR, Renin genetics, Renin metabolism, Renin-Angiotensin System drug effects, Renin-Angiotensin System genetics
- Abstract
Aims: Prevention of human hypertension is an important challenge and has been achieved in experimental models. Brief treatment with renin-angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this fascinating phenomenon, but relevant changes in gene expression are unknown., Methods and Results: In SHR, we studied the effect of treatment between 10 and 14 weeks of age with the angiotensin receptor blocker, losartan, or the angiotensin-converting enzyme inhibitor, perindopril [with controls for non-specific effects of lowering blood pressure (BP)], on differential RNA expression, DNA methylation, and renin immunolabelling in the kidney at 20 weeks of age. RNA sequencing revealed a six-fold increase in renin gene (Ren) expression during losartan treatment (P < 0.0001). Six weeks after losartan, arterial pressure remained lower (P = 0.006), yet kidney Ren showed reduced expression by 23% after losartan (P = 0.03) and by 43% after perindopril (P = 1.4 × 10-6) associated with increased DNA methylation (P = 0.04). Immunolabelling confirmed reduced cortical renin after earlier RAS blockade (P = 0.002). RNA sequencing identified differential expression of mRNAs, miRNAs, and lncRNAs with evidence of networking and co-regulation. These included 13 candidate genes (Grhl1, Ammecr1l, Hs6st1, Nfil3, Fam221a, Lmo4, Adamts1, Cish, Hif3a, Bcl6, Rad54l2, Adap1, Dok4), the miRNA miR-145-3p, and the lncRNA AC115371. Gene ontogeny analyses revealed that these networks were enriched with genes relevant to BP, RAS, and the kidneys., Conclusion: Early RAS inhibition in SHR resets genetic pathways and networks resulting in a legacy of reduced Ren expression and BP persisting for a minimum of 6 weeks., Competing Interests: Conflict of interest: There are no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2024
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29. Reviving Decades-Old Wisdom: Longitudinal Analysis of Renin-Angiotensin System Inhibitors and Its Effects on Acute Ischemic Stroke to Improve Outcomes.
- Author
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Samuel S, Craver K, Miller C, Pelsue B, Gonzalez C, Allison TA, Gulbis B, Choi HA, and Kim S
- Subjects
- Humans, Male, Female, Aged, Middle Aged, Longitudinal Studies, Treatment Outcome, Antihypertensive Agents therapeutic use, Adrenergic beta-Antagonists therapeutic use, Aged, 80 and over, Risk Factors, Time Factors, Drug Therapy, Combination, Hypertension drug therapy, Hypertension mortality, Hypertension physiopathology, Cross-Sectional Studies, Blood Pressure drug effects, Angiotensin Receptor Antagonists therapeutic use, Risk Assessment, Renin-Angiotensin System drug effects, Ischemic Stroke mortality, Ischemic Stroke drug therapy, Ischemic Stroke blood, Ischemic Stroke diagnosis, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Hospital Mortality
- Abstract
Background: While renin-angiotensin system (RAS) inhibitors have a longstanding history in blood pressure control, their suitability as first-line in-patient treatment may be limited due to prolonged half-life and kidney failure concerns., Methods: Using a cohort design, we assessed the impact of RAS inhibitors, either alone or in combination with beta-blockers, on mortality, while exploring interactions, including those related to end-stage renal disease and serum creatinine levels. Eligible subjects were Acute Ischemic Stroke (AIS) patients aged 18 or older with specific subtypes who received in-patient antihypertensive treatment. The primary outcome was mortality rates. Statistical analyses included cross-sectional and longitudinal approaches, employing generalized linear models, G-computation, and discrete-time survival analysis over a 20-day follow-up period., Results: In our study of 3,058 AIS patients, those using RAS inhibitors had significantly lower in-hospital mortality (2.2%) compared to non-users (12.1%), resulting in a relative risk (RR) of 0.18 (95% CI: 0.12-0.26). Further analysis using G-computation revealed a marked reduction in mortality risk associated with RAS inhibitors (0.0281 vs. 0.0913, risk difference [RD] of 6.31% or 0.0631, 95% CI: 0.046-0.079). Subgroup analysis demonstrated notable benefits, with individuals having creatinine levels below and above 1.3 mg/dl exhibiting statistically significant RD (RD -0.0510 vs. -0.0895), and a significant difference in paired comparison (-0.0385 or 3.85%, CI 0.023-0.054). Additionally, longitudinal analysis confirmed a consistent daily reduction of 0.93% in mortality risk associated with the intake of RAS inhibitors., Conclusions: RAS inhibitors are associated with a significant reduction in in-hospital mortality in AIS patients, suggesting potential clinical benefits in improving patient outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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30. Inhibition of the Renin-Angiotensin System Improves Response to Neoadjuvant Therapy in Patients With Liver Metastasis of Colorectal Cancers.
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Wirsik NM, Appel PC, Braun A, Strowitzki MJ, Schleussner N, Nienhüser H, Schneider M, and Schmidt T
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- Humans, Female, Male, Middle Aged, Aged, Retrospective Studies, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hepatectomy, Treatment Outcome, Bevacizumab therapeutic use, Bevacizumab administration & dosage, Chemotherapy, Adjuvant methods, Angiogenesis Inhibitors therapeutic use, Angiogenesis Inhibitors administration & dosage, Colorectal Neoplasms pathology, Colorectal Neoplasms drug therapy, Colorectal Neoplasms therapy, Liver Neoplasms secondary, Liver Neoplasms drug therapy, Liver Neoplasms therapy, Neoadjuvant Therapy methods, Renin-Angiotensin System drug effects
- Abstract
Introduction: Renin-angiotensin-aldosterone system inhibitors (RAAS-I) have been shown to prolong overall survival in patients with liver metastasized colorectal cancer in combination with antiangiogenic treatment. The effects of RAAS-I combined with neoadjuvant chemotherapy on colorectal cancer liver metastasis remain unexplored. We aimed to study the response of patients undergoing liver resection to RAAS-I in combination with neoadjuvant therapy to elucidate their potential benefits., Methods: Between February 2005 and May 2012, 62 patients fulfilled the inclusion criteria for distant metastasis (cM1) and comparable computed tomography or magnetic resonance tomography scans in the Picture Archiving Communication System of our center before and after neoadjuvant chemotherapy. Follow-up data and clinicopathological characteristics were collected from a prospective database and retrospectively investigated. The chemotherapeutic response to liver metastasis was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria 1.1., Results: Comparing the average reduction of measured lesions, a significant response to chemotherapy was detected in the patients receiving RAAS-I (n = 24) compared to those who did not (n = 38) (P = 0.031). Interestingly, the effect was more distinctive when the size reduction was compared between high responses with more than 50% size reduction of all measured lesions (P = 0.011). In the subgroup analysis of patients receiving bevacizumab treatment, high responses to chemotherapy were observed only in the RAAS-I cohort (28.6% versus 0%, P = 0.022)., Conclusions: For neoadjuvantly treated patients, concomitant antihypertensive treatment with RAAS-I showed a higher total size reduction of liver metastasis as a sign of treatment response, especially in combination with antiangiogenic treatment with bevacizumab., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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31. Renin-angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?
- Author
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de Cavanagh EMV, Inserra F, and Ferder L
- Subjects
- Humans, Animals, Signal Transduction drug effects, Mitochondria metabolism, Mitochondria drug effects, Angiotensin Receptor Antagonists pharmacology, Angiotensin Receptor Antagonists therapeutic use, Renin-Angiotensin System drug effects, Aging drug effects, Aging metabolism, Aging physiology, Angiotensin-Converting Enzyme Inhibitors pharmacology, Angiotensin-Converting Enzyme Inhibitors therapeutic use
- Abstract
The renin-angiotensin system (RAS)-a classical blood pressure regulator-largely contributes to healthy organ development and function. Besides, RAS activation promotes age-related changes and age-associated diseases, which are attenuated/abolished by RAS-blockade in several mammalian species. RAS-blockers also increase rodent lifespan. In previous work, we discussed how RAS-blockade downregulates mTOR and growth hormone/IGF-1 signaling, and stimulates AMPK activity (together with klotho, sirtuin, and vitamin D-receptor upregulation), and proposed that at least some of RAS-blockade's aging benefits are mediated through regulation of these intermediaries and their signaling to mitochondria. Here, we included RAS-blockade's impact on other aging regulatory pathways, that is, TGF-ß, NF-kB, PI3K, MAPK, PKC, Notch, and Wnt, all of which affect mitochondria. No direct evidence is available on RAS/RAS-blockade-aging regulatory pathway-mitochondria interactions. However, existing results allow to conjecture that RAS-blockers neutralize mitochondrial dysfunction by acting on the discussed pathways. The reviewed evidence led us to propose that the foundation is laid for conducting clinical trials aimed at testing whether angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)-even at subclinical doses-offer the possibility to live longer and in better health. As ACEi and ARB are low cost and well-tolerated anti-hypertension therapies in use for over 35 years, investigating their administration to attenuate/prevent aging effects seems simple to implement., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
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- 2024
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32. Delayed Graft Function and the Renin-angiotensin System.
- Author
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Yamani F, Cianfarini C, and Batlle D
- Subjects
- Humans, Animals, Acute Kidney Injury etiology, Acute Kidney Injury physiopathology, Acute Kidney Injury metabolism, Angiotensin-Converting Enzyme 2 metabolism, Renin-Angiotensin System physiology, Kidney Transplantation adverse effects, Delayed Graft Function etiology, Delayed Graft Function physiopathology
- Abstract
Delayed graft function (DGF) is a form of acute kidney injury (AKI) and a common complication following kidney transplantation. It adversely influences patient outcomes increases the financial burden of transplantation, and currently, no specific treatments are available. In developing this form of AKI, activation of the renin-angiotensin system (RAS) has been proposed to play an important role. In this review, we discuss the role of RAS activation and its contribution to the pathophysiology of DGF following the different stages of the transplantation process, from procurement and ischemia to transplantation into the recipient and including data from experimental animal models. Deceased kidney donors, whether during cardiac or brain death, may experience activation of the RAS. That may be continued or further potentiated during procurement and organ preservation. Additional evidence suggests that during implantation of the kidney graft and reperfusion in the recipient, the RAS is activated and may likely remain activated, extrapolating from other forms of AKI where RAS overactivity is well documented. Of particular interest in this setting is the status of angiotensin-converting enzyme 2, a key RAS enzyme essential for the metabolism of angiotensin II and abundantly present in the apical border of the proximal tubules, which is the site of predominant injury in AKI and DGF. Interventions aimed at safely downregulating the RAS using suitable shorter forms of angiotensin-converting enzyme 2 could be a way to offer protection against DGF., Competing Interests: D.B. is a consultant for AstraZeneca, Renibus, and Advicenne; has ownership interest in Angiotensin Therapeutics Inc; received research funding from AstraZeneca, Feinberg Foundation, and the National Institutes of Health; and patents or royalties and founder of Angiotensin Therapeutics Inc. D.B. is the coinventor of patents: “Active Low Molecular Weight Variants of Angiotensin Converting Enzyme 2” and “Soluble ACE2 variants and uses therefore.” The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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33. The Renin-Angiotensin System in Liver Disease.
- Author
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McGrath MS and Wentworth BJ
- Subjects
- Humans, Animals, Liver Cirrhosis metabolism, Liver Cirrhosis pathology, Renin-Angiotensin System physiology, Liver Diseases metabolism, Liver Diseases pathology
- Abstract
The renin-angiotensin system (RAS) is a complex homeostatic entity with multiorgan systemic and local effects. Traditionally, RAS works in conjunction with the kidney to control effective arterial circulation, systemic vascular resistance, and electrolyte balance. However, chronic hepatic injury and resulting splanchnic dilation may disrupt this delicate balance. The role of RAS in liver disease, however, is even more extensive, modulating hepatic fibrosis and portal hypertension. Recognition of an alternative RAS pathway in the past few decades has changed our understanding of RAS in liver disease, and the concept of opposing vs. "rebalanced" forces is an ongoing focus of research. Whether RAS inhibition is beneficial in patients with chronic liver disease appears to be context-dependent, but further study is needed to optimize clinical management and reduce organ-specific morbidity and mortality. This review presents the current understanding of RAS in liver disease, acknowledges areas of uncertainty, and describes potential areas of future investigation.
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- 2024
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34. Alternative Renin-Angiotensin System.
- Author
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Bader M, Steckelings UM, Alenina N, Santos RAS, and Ferrario CM
- Subjects
- Angiotensin I metabolism, Peptide Fragments metabolism, Peptides, Peptidyl-Dipeptidase A metabolism, Receptors, G-Protein-Coupled metabolism, Renin, Humans, Angiotensin II, Renin-Angiotensin System physiology
- Abstract
The renin-angiotensin system is the most important peptide hormone system in the regulation of cardiovascular homeostasis. Its classical arm consists of the enzymes, renin, and angiotensin-converting enzyme, generating angiotensin II from angiotensinogen, which activates its AT
1 receptor, thereby increasing blood pressure, retaining salt and water, and inducing cardiovascular hypertrophy and fibrosis. However, angiotensin II can also activate a second receptor, the AT2 receptor. Moreover, the removal of the C-terminal phenylalanine from angiotensin II by ACE2 (angiotensin-converting enzyme 2) yields angiotensin-(1-7), and this peptide interacts with its receptor Mas. When the aminoterminal Asp of angiotensin-(1-7) is decarboxylated, alamandine is generated, which activates the Mas-related G-protein-coupled receptor D, MrgD (Mas-related G-protein-coupled receptor type D). Since Mas, MrgD, and the AT2 receptor have opposing effects to the classical AT1 receptor, they and the enzymes and peptides activating them are called the alternative or protective arm of the renin-angiotensin system. This review will cover the historical aspects and the current standing of this recent addition to the biology of the renin-angiotensin system., Competing Interests: Disclosures None.- Published
- 2024
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35. The role of the brain renin-angiotensin system in Parkinson´s disease.
- Author
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Labandeira-Garcia JL, Labandeira CM, Guerra MJ, and Rodriguez-Perez AI
- Subjects
- Animals, Humans, Angiotensin Receptor Antagonists pharmacology, Angiotensins metabolism, Blood Pressure, Brain metabolism, Dopamine, Receptor, Angiotensin, Type 1 metabolism, Parkinson Disease pathology, Renin-Angiotensin System physiology
- Abstract
The renin-angiotensin system (RAS) was classically considered a circulating hormonal system that regulates blood pressure. However, different tissues and organs, including the brain, have a local paracrine RAS. Mutual regulation between the dopaminergic system and RAS has been observed in several tissues. Dysregulation of these interactions leads to renal and cardiovascular diseases, as well as progression of dopaminergic neuron degeneration in a major brain center of dopamine/angiotensin interaction such as the nigrostriatal system. A decrease in the dopaminergic function induces upregulation of the angiotensin type-1 (AT1) receptor activity, leading to recovery of dopamine levels. However, AT1 receptor overactivity in dopaminergic neurons and microglial cells upregulates the cellular NADPH-oxidase-superoxide axis and Ca
2+ release, which mediate several key events in oxidative stress, neuroinflammation, and α-synuclein aggregation, involved in Parkinson's disease (PD) pathogenesis. An intraneuronal antioxidative/anti-inflammatory RAS counteracts the effects of the pro-oxidative AT1 receptor overactivity. Consistent with this, an imbalance in RAS activity towards the pro-oxidative/pro-inflammatory AT1 receptor axis has been observed in the substantia nigra and striatum of several animal models of high vulnerability to dopaminergic degeneration. Interestingly, autoantibodies against angiotensin-converting enzyme 2 and AT1 receptors are increased in PD models and PD patients and contribute to blood-brain barrier (BBB) dysregulation and nigrostriatal pro-inflammatory RAS upregulation. Therapeutic strategies addressed to the modulation of brain RAS, by AT1 receptor blockers (ARBs) and/or activation of the antioxidative axis (AT2, Mas receptors), may be neuroprotective for individuals with a high risk of developing PD or in prodromal stages of PD to reduce progression of the disease., (© 2024. The Author(s).)- Published
- 2024
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36. Upregulation of the Renin-Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma.
- Author
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Lozinski M, Lumbers ER, Bowden NA, Martin JH, Fay MF, Pringle KG, and Tooney PA
- Subjects
- Humans, Up-Regulation genetics, Tumor Microenvironment, Receptors, Cell Surface metabolism, Prorenin Receptor, Renin-Angiotensin System genetics, Glioblastoma genetics
- Abstract
Glioblastoma is a highly aggressive disease with poor survival outcomes. An emerging body of literature links the role of the renin-angiotensin system (RAS), well-known for its function in the cardiovascular system, to the progression of cancers. We studied the expression of RAS-related genes ( ATP6AP2 , AGTR1 , AGTR2 , ACE , AGT , and REN ) in The Cancer Genome Atlas (TCGA) glioblastoma cohort, their relationship to patient survival, and association with tumour microenvironment pathways. The expression of RAS genes was then examined in 12 patient-derived glioblastoma cell lines treated with chemoradiation. In cases of glioblastoma within the TCGA, ATP6AP2 , AGTR1 , ACE , and AGT had consistent expressions across samples, while AGTR2 and REN were lowly expressed. High expression of AGTR1 was independently associated with lower progression-free survival (PFS) ( p = 0.01) and had a non-significant trend for overall survival (OS) after multivariate analysis ( p = 0.095). The combined expression of RAS receptors ( ATP6AP2 , AGTR1 , and AGTR2 ) was positively associated with gene pathways involved in hypoxia, microvasculature, stem cell plasticity, and the molecular characterisation of glioblastoma subtypes. In patient-derived glioblastoma cell lines, ATP6AP2 and AGTR1 were upregulated after chemoradiotherapy and correlated with an increase in HIF1A expression. This data suggests the RAS is correlated with changes in the tumour microenvironment and associated with glioblastoma survival outcomes.
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- 2024
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37. Is proteinuria an important fact concerning the nephroprotective effect of renin-angiotensin system inhibitors?
- Author
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Galceran JM
- Subjects
- Humans, Angiotensin-Converting Enzyme Inhibitors pharmacology, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Proteinuria prevention & control, Proteinuria drug therapy, Antihypertensive Agents pharmacology, Antihypertensive Agents therapeutic use, Renin-Angiotensin System
- Published
- 2024
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38. Continuation vs Discontinuation of Renin-Angiotensin System Inhibitors Before Major Noncardiac Surgery
- Author
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Legrand, Matthieu, Falcone, Jérémy, Cholley, Bernard, Charbonneau, Hélène, Delaporte, Amélie, Lemoine, Adrien, Garot, Matthias, Joosten, Alexandre, Meistelman, Claude, Cheron-Leroy, Delphine, Rives, Jean-Philippe, Pastene, Bruno, Dewitte, Antoine, Sigaut, Stéphanie, Danguy des Deserts, Marc, Truc, Cyrille, Boisson, Matthieu, Lasocki, Sigismond, Cuvillon, Philippe, Schiff, Ugo, Jaber, Samir, Le Guen, Morgan, Caillard, Anaïs, Bar, Stéphane, Pereira de Souza Neto, Edmundo, Colas, Vincent, Dimache, Florin, Girardot, Thibaut, Jozefowicz, Elsa, Viquesnel, Simon, Berthier, Francis, Vicaut, Eric, Gayat, Etienne, MONZIOLS, Simon, DEFAYE, Mylene, CAMUS, Thibault, ROBIN, Jean-Jacques, OUATTARA, Alexandre, FETITA, Ioana, JOANNES-BOYAU, Olivier, BONNARDEL, Eline, BOUQUEREL, Rémi, STRZELECKI, Antoine, FAYON, Thibaut, PELLETIER, Christophe, LE GAILLARD, Benjamin, GIRARDOT, Thibaut, AMOUSSOU, Géraud, EL BOUYOUSFI, Maalik, GANASCIA, Bruno, BUTRULLE, Calliope, GERGAUD, Soizic, HABRIAL, Pierre, PESSIOT, Solène, SAMSON, Emmanuel, WOLFF, Caroline, STANKOVA, Nevena, AOUATI, Farida, KAVAFYAN, Juliette, SUPARSCHI, Vlad, LONGROIS, Dan, LE ROY, Julie, ROSSIGNOL, Benoit, HUET, Olivier, BOISSON, Christophe, BONNIN, Pierre Olivier, DHAOUADI, Mohamed, GARDES, Ghislaine, PERIN, Mikael, BRUNET, Sophie, GRICOURT, Yann, FISCHER, Marc-Olivier, DEBROCZI, Stéphane, RETOURNAY, Lucie, STRUB, Pierre, VIVIN, Patrice, DUPAYS, Rachel, KERFORNE, Thomas, VIANET, Gabriel, MANZANO, Virginie, NOLL, Eric, LUDES, Pierre-Olivier, CHAMARAUX-TRAN, Thien-Nga, CIRENEI, Cédric, HAMROUN, Djihad, LEBAS, Benoit, ANDRIEU, Grégoire ANDRIEU, ETIENNE, Vincent, CINOTTI, Raphaël, SIMON, Natacha, FRASCA, Denis, BELOEIL, Hélène, LE GALL, Amandine, TECHEV, Petyo, MEURET, Ludovic, JOFFRE, Jérémie, DUPONT, Hervé, CHARBIT, Beny, DAVY, Arthur, and LOBO, David
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Patient Safety ,Cardiovascular ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,6.4 Surgery ,Oral and gastrointestinal ,Good Health and Well Being ,Stop-or-Not Trial Group ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
ImportanceBefore surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines.ObjectiveTo evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery.Design, setting, and participantsRandomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France.InterventionPatients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115).Main outcomes and measuresThe primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery.ResultsOf the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes.Conclusions and relevanceAmong patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy.Trial registrationClinicalTrials.gov Identifier: NCT03374449.
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- 2024
39. Interaction of estradiol and renin–angiotensin system with microRNAs-21 and -29 in renal fibrosis: focus on TGF-β/smad signaling pathway
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Rajabi, Soodeh, Saberi, Shadan, Najafipour, Hamid, Askaripour, Majid, Rajizadeh, Mohammad Amin, Shahraki, Sarieh, and Kazeminia, Sara
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- 2024
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40. The impact of Renin-Angiotensin System Inhibitors on bone fracture risk: a nationwide nested case-control study
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Kim, Kwang Min, Hwang, Eun Jung, Lee, Sangjin, and Yoon, Jeong-Hyun
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- 2024
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41. Sex differences in fetal kidney reprogramming: the case in the renin-angiotensin system
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Pérez-Coria, Mariana, Vázquez-Rivera, Gloria Elizabeth, Gómez-García, Erika Fabiola, and Mendoza-Carrera, Francisco
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- 2024
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42. Diverse biological functions of the renin-angiotensin system.
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Rao A, Bhat SA, Shibata T, Giani JF, Rader F, Bernstein KE, and Khan Z
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- Humans, Angiotensin II metabolism, Peptidyl-Dipeptidase A metabolism, Renin-Angiotensin System physiology, Kidney metabolism
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The renin-angiotensin system (RAS) has been widely known as a circulating endocrine system involved in the control of blood pressure. However, components of RAS have been found to be localized in rather unexpected sites in the body including the kidneys, brain, bone marrow, immune cells, and reproductive system. These discoveries have led to steady, growing evidence of the existence of independent tissue RAS specific to several parts of the body. It is important to understand how RAS regulates these systems for a variety of reasons: It gives a better overall picture of human physiology, helps to understand and mitigate the unintended consequences of RAS-inhibiting or activating drugs, and sets the stage for potential new therapies for a variety of ailments. This review fulfills the need for an updated overview of knowledge about local tissue RAS in several bodily systems, including their components, functions, and medical implications., (© 2023 Wiley Periodicals LLC.)
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- 2024
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43. The alternative renin-angiotensin system in critically ill patients: pathophysiology and therapeutic implications.
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Garcia, Bruno, Zarbock, Alexander, Bellomo, Rinaldo, and Legrand, Matthieu
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Acute kidney injury ,Acute lung injury ,Acute respiratory distress syndrome ,Angiotensin II ,Angiotensin-(1–7) ,Angiotensin-converting enzyme 2 ,Dipeptidyl-peptidase 3 ,Shock ,Humans ,Renin-Angiotensin System ,Angiotensin-Converting Enzyme 2 ,Critical Illness ,Angiotensin II ,Acute Lung Injury - Abstract
The renin-angiotensin system (RAS) plays a crucial role in regulating blood pressure and the cardio-renal system. The classical RAS, mainly mediated by angiotensin I, angiotensin-converting enzyme, and angiotensin II, has been reported to be altered in critically ill patients, such as those in vasodilatory shock. However, recent research has highlighted the role of some components of the counterregulatory axis of the classical RAS, termed the alternative RAS, such as angiotensin-converting Enzyme 2 (ACE2) and angiotensin-(1-7), or peptidases which can modulate the RAS like dipeptidyl-peptidase 3, in many critical situations. In cases of shock, dipeptidyl-peptidase 3, an enzyme involved in the degradation of angiotensin and opioid peptides, has been associated with acute kidney injury and mortality and preclinical studies have tested its neutralization. Angiotensin-(1-7) has been shown to prevent septic shock development and improve outcomes in experimental models of sepsis. In the context of experimental acute lung injury, ACE2 activity has demonstrated a protective role, and its inactivation has been associated with worsened lung function, leading to the use of active recombinant human ACE2, in preclinical and human studies. Angiotensin-(1-7) has been tested in experimental models of acute lung injury and in a recent randomized controlled trial for patients with COVID-19 related hypoxemia. Overall, the alternative RAS appears to have a role in the pathogenesis of disease in critically ill patients, and modulation of the alternative RAS may improve outcomes. Here, we review the available evidence regarding the methods of analysis of the RAS, pathophysiological disturbances of this system, and discuss how therapeutic manipulation may improve outcomes in the critically ill.
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- 2023
44. The Intriguing Connection between Cholestasis and the Renin-Angiotensin System Dysregulation Induced by SARS-CoV-2 and/or the Vaccinal Spike Protein.
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Fajloun Z, Khattar ZA, and Sabatier JM
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- Humans, COVID-19 Vaccines adverse effects, Renin-Angiotensin System physiology, COVID-19 complications, Spike Glycoprotein, Coronavirus metabolism, SARS-CoV-2, Cholestasis
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- 2024
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45. Zamzam Water Mitigates Cardiac Toxicity Risk through Modulation of GUT Microbiota and the Renin-angiotensin System.
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Sheikh RA, Nadem MS, Asar TO, Almujtaba MA, Naqvi S, Al-Abbasi FA, Almalki NAR, Kumar V, and Anwar F
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- Animals, Male, Rats, Doxorubicin pharmacology, Water chemistry, Gastrointestinal Microbiome drug effects, Renin-Angiotensin System drug effects
- Abstract
Background: Cardiovascular diseases (CVDs) continue to exert a substantial global influence in specific areas due to population growth, aging, microbiota, and genetic/environmental factors. Drinking water has a strong impact on the health of an individual. Further, emerging evidence has highlighted the therapeutic potential and benefits of Zamzam water (Zam)., Objective: We investigated the influence of Zam on doxorubicin-induced cardiac toxicity, elucidating its consequential effects on GUT microbiota dysbiosis and hepatic and renal functions., Methods: Male rats were categorized into four groups: Group 1 as Normal control (NC), Group 2 as Zamzam control (ZC), Group 3 Disease control (DC) and Group 4 as Therapeutic control (DZ) treated with Zam against doxorubicin-induced disease at a dose of 1mg/kg boy weight) intraperitoneally (i.p)., Results: Significant dysbiosis in the composition of GM was observed in the DC group along with a significant decrease (p < 0.05) in serum levels of Zinc, interleukin-10 (IL-10), IL-6 and Angiotensin II (Ang II), while C-reactive protein (CRP), fibrinogen, and CKMB increased significantly (restoration of Zinc ions (0.72 ± 0.07 mcg/mL) compared to NC. Treatment with Zamzam exhibited a marked abundance of 18-times to 72% in Romboutsia, a genus of firmicutes, along with lowering of Proteobacteria in DZ followed by significant restoration of Zinc ions (0.72 ± 0.07 mcg/mL), significant (p ˂ 0.05) reduction in CRP (7.22 ± 0.39 mg/dL), CKMB (118.8 ± 1.02 U/L) and Fibrinogen (3.18 ± 0.16 mg/dL), significant (p < 0.05) increase in IL-10 (7.22 ± 0.84 pg/mL) and IL-6 (7.18 ± 0.40 pg/ml), restoration of Ang II (18.62 ± 0.50 nmol/mL/min), marked increase in renin with normal myocyte architecture and tissue orientation of kidney, and restoration of histological architecture of hepatocyte., Conclusion: Zam treatment mitigated cardiac toxicity risk through the modulation of GUT microbiota and the renin-angiotensin system and tissue histology effectively., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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46. Signaling pathways and genetics of brain Renin angiotensin system in psychiatric disorders: State of the art.
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Barak R, Goshtasbi G, Fatehi R, and Firouzabadi N
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- Humans, Peptidyl-Dipeptidase A metabolism, Signal Transduction genetics, Peptide Fragments metabolism, Brain metabolism, Angiotensin II metabolism, Receptors, G-Protein-Coupled metabolism, Renin-Angiotensin System genetics, Mental Disorders genetics
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Along the conventional pathways, Renin-angiotensin system (RAS) plays a key role in the physiology of the CNS and pathogenesis of psychiatric diseases. RAS is a complex regulatory pathway which is composed of several peptides and receptors and comprises two counter-regulatory axes. The classical (ACE1/AngII/AT1 receptor) axis and the contemporary (ACE2/Ang (1-7)/Mas receptor) axis. The genes coding for elements of both axes have been broadly studied. Numerous functional polymorphisms on components of RAS have been identified to serve as informative disease and treatment markers. This review summarizes the role of each peptide and receptor in the pathophysiology of psychiatric disorders (depression, bipolar disorders and schizophrenia), followed by a concise look at the role of genetic polymorphism of the RAS in the pathophysiology of these disorders., (Copyright © 2023. Published by Elsevier Inc.)
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- 2024
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47. A longitudinal study on the effect of obesity upon circulating renin-angiotensin system in normal pregnancy.
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Bernardi S, Tonon F, Barbieri M, Zamagni G, Nuredini R, Perer L, Comar S, Toffoli B, Ronfani L, Ricci G, Fabris B, and Stampalija T
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- Female, Humans, Infant, Newborn, Pregnancy, Enzyme-Linked Immunosorbent Assay, Longitudinal Studies, Placenta, Renin-Angiotensin System, Obesity, Maternal blood, Angiotensinogen blood, Renin blood
- Abstract
Background and Aims: Obesity is the most common health issue in women of reproductive age, which profoundly affects maternal-fetal health. Despite progress in understanding key inflammatory and metabolic changes, the pathogenesis of the cardiovascular phenotype of obese pregnant women remains to be fully understood. This study aimed at: (i) evaluating the changes of the renin-angiotensin system (RAS) throughout pregnancy in obese vs normal weight (control) women, and (ii) evaluating the presence of any associations between maternal hemodynamic status and RAS changes., Methods and Results: Thirty-eight normal weight and nineteen obese pregnant women were included. Clinical assessment, blood samples and maternal hemodynamic evaluation were performed at 12, 20, 30, and 36 weeks, while ultrasound assessment was scheduled at 20, 30, and 36 weeks of gestation. Measurements of sFlt-1, PlGF, Angiotensinogen, Renin, AngII, Ang1-7, ACE and ACE2 were performed by ELISA. Our data show that normotensive obese women had lower placental blood supply, as assessed by UV-Q and UV-Q/EFW, as compared to controls, and significantly higher levels of AngII and AngII/Ang1-7 ratio, which were inversely related to placental blood supply., Conclusions: Our study shows for the first time that normotensive obese women exhibited a significant progressive increase of AngII and AngII/Ang1-7 throughout pregnancy, which were inversely related to placental blood supply as assessed by UV-Q and UV-Q/EFW. Our data shed light on the early changes in pregnant obese women and suggest that RAS dysregulation is a prerequisite rather than a consequence of hypertensive disorders of pregnancy and other maternal neonatal complications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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48. Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system.
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Zhao BW, Chen YJ, Zhang RP, Chen YM, and Huang BW
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- Animals, Mice, Angiotensin II metabolism, Angiotensin-Converting Enzyme 2, Fibrosis, Hepatic Stellate Cells metabolism, Liver Cirrhosis, Peptidyl-Dipeptidase A metabolism, Renin-Angiotensin System
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The present letter to the editor is related to the study titled ' Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells'. Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2024
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49. Partial Replacement of NaCl with KCl in Cooked Meat Could Reduce the Liver Damage Through Renin-Angiotensin System in Mice.
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Zou L, Yu X, Xiong J, Chen C, and Xiao G
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- Animals, Mice, Potassium Chloride pharmacology, Potassium Chloride metabolism, Sodium Chloride, Dietary pharmacology, Angiotensin II pharmacology, Meat, Liver metabolism, Sodium pharmacology, Renin-Angiotensin System, Sodium Chloride pharmacology, Sodium Chloride metabolism
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Scope: Dietary salt (sodium chloride, NaCl) is necessary for processed meat products, but intake of a high-sodium diet carries serious health risks. Considerable studies indicate that the partial substitution of NaCl with potassium chloride (KCl) can produce sodium-reduced cooked meat. However, most studies of sodium-reduced cooked meat focus on the production process in vitro, and the effect of cooked meat on health has not been well clarified in vivo., Methods and Results: This study finds that compared to the high-sodium group (HS), serum renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and the levels of some indicators of dyslipidemia are decreased in the reduced salt by partial substitution of NaCl with KCl group (RS + K). Furthermore, RS + K increases the antioxidation abilities, inhibits the renin-angiotensin system (RAS) through ACE/Ang II/Ang II type 1 receptor axis pathway, reduces synthesis of triglyceride and cholesterol and protein expressions of inflammatory factors interleukin-17A and nuclear factor-kappa B in the liver., Conclusion: Partial substitution of NaCl with KCl in cooked meat can be a feasible approach for improving the health benefits and developing novel functional meat products for nutritional health interventions., (© 2024 Wiley-VCH GmbH.)
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- 2024
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50. Effect of Renin-Angiotensin System Blockers in Acute Myocardial Infarction Patients with Acute Kidney Injury.
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Kim KA, Lee JE, Choi IJ, Lee KY, Kim CJ, Park MW, Park CS, Kim HY, Yoo KD, Jeon DS, Jeong MH, and Chang K
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- Humans, Male, Female, Aged, Middle Aged, Republic of Korea epidemiology, Registries, Angiotensin Receptor Antagonists therapeutic use, Creatinine blood, Treatment Outcome, Acute Kidney Injury etiology, Myocardial Infarction complications, Myocardial Infarction drug therapy, Renin-Angiotensin System drug effects, Percutaneous Coronary Intervention, Angiotensin-Converting Enzyme Inhibitors therapeutic use
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Introduction: Renin-angiotensin system blockers (RASBs) are known to improve mortality after acute myocardial infarction (AMI). However, there remain uncertainties regarding treatment with RASBs after AMI in patients with renal dysfunction and especially in the setting of acute kidney injury (AKI)., Methods: Patients from a multicenter AMI registry undergoing percutaneous coronary intervention in Korea were stratified and analyzed according to the presence of AKI, defined as an increase in serum creatinine levels of ≥0.3 mg/dL or ≥50% increase from baseline during admission, and RASB prescription at discharge. The primary outcome of interest was 5-year all-cause mortality., Results: In total 9,629 patients were selected for initial analysis, of which 2,405 had an episode of AKI. After adjustment using multivariable Cox regression, treatment with RASBs at discharge was associated with decreased all-cause mortality in the entire cohort (hazard ratio [HR] 0.849, confidence interval [CI] 0.753-0.956), but not for the patients with AKI (HR 0.988, CI 0.808-1.208). In subgroup analysis, RASBs reduced all-cause mortality in patients with stage I AKI (HR 0.760, CI 0.584-0.989) but not for stage II and III AKI (HR 1.200, CI 0.899-1.601, interaction p value 0.002). Similar heterogeneities between RASB use and AKI severity were also observed for other clinical outcomes of interest., Conclusion: Treatment with RASBs in patients with AMI and concomitant AKI is associated with favorable outcomes in non-severe AKI, but not in severe AKI. Further studies to confirm these results and to develop strategies to minimize the occurrence of adverse effects arising from RASB treatment are needed., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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