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Advances in Biological Regulation Aug 2021The article describes the possible pathophysiological origin of COVID-19 and the crucial role of renin-angiotensin system (RAS), providing several "converging" evidence... (Review)
Review
The article describes the possible pathophysiological origin of COVID-19 and the crucial role of renin-angiotensin system (RAS), providing several "converging" evidence in support of this hypothesis. SARS-CoV-2 has been shown to initially upregulate ACE2 systemic activity (early phase), which can subsequently induce compensatory responses leading to upregulation of both arms of the RAS (late phase) and consequently to critical, advanced and untreatable stages of COVID-19 disease. The main and initial actors of the process are ACE2 and ADAM17 zinc-metalloproteases, which, initially triggered by SARS-CoV-2 spike proteins, work together in increasing circulating Ang 1-7 and Ang 1-9 peptides and downstream (Mas and Angiotensin type 2 receptors) pathways with anti-inflammatory, hypotensive and antithrombotic activities. During the late phase of severe COVID-19, compensatory secretion of renin and ACE enzymes are subsequently upregulated, leading to inflammation, hypertension and thrombosis, which further sustain ACE2 and ADAM17 upregulation. Based on this hypothesis, COVID-19-phase-specific inhibition of different RAS enzymes is proposed as a pharmacological strategy against COVID-19 and vaccine-induced adverse effects. The aim is to prevent the establishment of positive feedback-loops, which can sustain hyperactivity of both arms of the RAS independently of viral trigger and, in some cases, may lead to Long-COVID syndrome.
Topics: ADAM17 Protein; Angiotensin I; Angiotensin-Converting Enzyme 2; COVID-19; Gene Expression Regulation, Enzymologic; Humans; Peptide Fragments; Renin-Angiotensin System; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Up-Regulation; COVID-19 Drug Treatment
PubMed: 34419773
DOI: 10.1016/j.jbior.2021.100820 -
Cells May 2020The renin-angiotensin system (RAS) is a network of proteins regulating many aspects of human physiology, including cardiovascular, pulmonary, and immune system... (Review)
Review
The renin-angiotensin system (RAS) is a network of proteins regulating many aspects of human physiology, including cardiovascular, pulmonary, and immune system physiology. The RAS is a complicated network of G-protein coupled receptors (GPCRs) (i.e., AT1R, AT2R, MASR, and MRGD) orchestrating the effects of several hormones (i.e., angiotensin II, angiotensin (1-7), and alamandine) produced by protease-based transmembrane receptors (ACE1 and ACE2). Two signaling axes have been identified in the RAS endocrine system that mediate the proliferative actions of angiotensin II (i.e., the AT1R-based pathway) or the anti-proliferative effects of RAS hormones (i.e., the AT2R-, MAS-, and MRGD-based pathways). Disruption of the balance between these two axes can cause different diseases (e.g., cardiovascular pathologies and the severe acute respiratory syndrome coronavirus 2- (SARS-CoV-2)-based COVID-19 disease). It is now accepted that all the components of the RAS endocrine system are expressed in cancer, including cancer of the breast. Breast cancer (BC) is a multifactorial pathology for which there is a continuous need to identify novel drugs. Here, I reviewed the possible roles of both axes of the RAS endocrine network as potential druggable pathways in BC. Remarkably, the analysis of the current knowledge of the different GPCRs of the RAS molecular system not only confirms that AT1R could be considered a drug target and that its inhibition by losartan and candesartan could be useful in the treatment of BC, but also identifies Mas-related GPCR member D (MRGD) as a druggable protein. Overall, the RAS of GPCRs offers multifaceted opportunities for the development of additional compounds for the treatment of BC.
Topics: Angiotensin I; Angiotensin II; Breast Neoplasms; Female; Humans; Peptide Fragments; Proto-Oncogene Mas; Proto-Oncogene Proteins; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, G-Protein-Coupled; Renin-Angiotensin System
PubMed: 32471115
DOI: 10.3390/cells9061336 -
Critical Care Clinics Apr 2019Classic and nonclassic renin-angiotensin systems (RAS) are 2 sides of an ubiquitous endocrine/paracrine cascade regulating blood pressure and homeostasis. Angiotensin II... (Review)
Review
Classic and nonclassic renin-angiotensin systems (RAS) are 2 sides of an ubiquitous endocrine/paracrine cascade regulating blood pressure and homeostasis. Angiotensin II and angiotensin-converting enzyme (ACE) levels are associated with severity of disease in the critically ill, and are central to the physiology and the pathogenesis of circulatory shock. Angiotensin (1-7) and ACE2 act as an endogenous counterregulatory arm to the angiotensin II/ACE axis. The tissue-based RAS has paracrine effects dissociated from those of the circulating RAS. Exogenous angiotensin II or ACE2 may improve the outcome of septic shock and acute respiratory distress syndrome, respectively.
Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Angiotensin I; Angiotensin II; Blood Pressure; Critical Illness; Female; Homeostasis; Humans; Male; Middle Aged; Peptide Fragments; Renin-Angiotensin System; Respiratory Distress Syndrome; Shock, Septic; Vasoconstrictor Agents
PubMed: 30784605
DOI: 10.1016/j.ccc.2018.11.002 -
Experimental Physiology Jun 2017
Review
Topics: Angiotensin I; Angiotensin II; Animals; Chronic Disease; Exercise; Humans; Muscle, Skeletal; Weight Loss
PubMed: 28568964
DOI: 10.1113/EP086216 -
Advances in Experimental Medicine and... 2019The rennin-angiotensin-aldosterone system (RAAS) has been well documented in regulating blood pressure, fluid volume, and sodium balance. Overactivity of RAAS promotes... (Review)
Review
The rennin-angiotensin-aldosterone system (RAAS) has been well documented in regulating blood pressure, fluid volume, and sodium balance. Overactivity of RAAS promotes both systemic and regional glomerular capillary hypertension, which could induce hemodynamic injury to the glomerulus, leading to kidney damage and renal fibrosis via profibrotic and proinflammatory pathway. Therefore, the use of RAAS inhibitors (i.e., ACEIs, ARBs, and MRAs) as the optional therapy has been demonstrated to prevent proteinuria, and kidney fibrosis and slow the decline of renal function effectively in the process of kidney disease during the last few decades. Recently, several new components of the RAAS have been discovered, including ACE2 and the corresponding ACE2/Ang (1-7)/Mas axis, which are also present in the kidney. Besides the classic RAAS inhibitors target the angiotensin-AT1-aldosterone axis, with the expanding knowledge about RAAS, a number of potential therapeutic targets in this system is emerging. Newer agents that are more specific are being developed. The present chapter outlines the insights of the RAAS agents (classic RAAS antagonists/the new RAAS drugs), and discusses its clinical application in the combat of renal fibrosis.
Topics: Aldosterone; Angiotensin I; Blood Pressure; Humans; Hypertension; Mineralocorticoid Receptor Antagonists; Renin-Angiotensin System
PubMed: 31399990
DOI: 10.1007/978-981-13-8871-2_33 -
Bioscience Reports Sep 2019The renin-angiotensin system (RAS) is undisputedly well-studied as one of the oldest and most critical regulators for arterial blood pressure, fluid volume, as well as... (Review)
Review
The renin-angiotensin system (RAS) is undisputedly well-studied as one of the oldest and most critical regulators for arterial blood pressure, fluid volume, as well as renal function. In recent studies, RAS has also been implicated in the development of obesity, diabetes, hyperlipidemia, and other diseases, and also involved in the regulation of several signaling pathways such as proliferation, apoptosis and autophagy, and insulin resistance. AMP-activated protein kinase (AMPK), an essential cellular energy sensor, has also been discovered to be involved in these diseases and cellular pathways. This would imply a connection between the RAS and AMPK. Therefore, this review serves to draw attention to the cross-talk between RAS and AMPK, then summering the most recent literature which highlights AMPK as a point of balance between physiological and pathological functions of the RAS.
Topics: AMP-Activated Protein Kinases; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Autophagy; Blood Pressure; Blood Vessels; Gene Expression Regulation; Humans; Insulin Resistance; Kidney; Muscle, Skeletal; Myocardium; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System; Signal Transduction
PubMed: 31413168
DOI: 10.1042/BSR20181994 -
Current Hypertension Reports Jul 2020To review recent data that suggest opposing effects of brain angiotensin type-1 (ATR) and type-2 (ATR) receptors on blood pressure (BP). Here, we discuss recent studies... (Review)
Review
PURPOSE OF REVIEW
To review recent data that suggest opposing effects of brain angiotensin type-1 (ATR) and type-2 (ATR) receptors on blood pressure (BP). Here, we discuss recent studies that suggest pro-hypertensive and pro-inflammatory actions of ATR and anti-hypertensive and anti-inflammatory actions of ATR. Further, we propose mechanisms for the interplay between brain angiotensin receptors and neuroinflammation in hypertension.
RECENT FINDINGS
The renin-angiotensin system (RAS) plays an important role in regulating cardiovascular physiology. This includes brain ATR and ATR, both of which are expressed in or adjacent to brain regions that control BP. Activation of ATR within those brain regions mediate increases in BP and cause neuroinflammation, which augments the BP increase in hypertension. The fact that ATR and ATR have opposing actions on BP suggests that ATR and ATR may have similar opposing actions on neuroinflammation. However, the mechanisms by which brain ATR and ATR mediate neuroinflammatory responses remain unclear. The interplay between brain angiotensin receptor subtypes and neuroinflammation exacerbates or protects against hypertension.
Topics: Angiotensin I; Brain; Humans; Hypertension; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin
PubMed: 32661792
DOI: 10.1007/s11906-020-01062-0 -
Journal of the American Society of... May 2017Inappropriate activation of the renin-angiotensin system (RAS) exacerbates renal and vascular injury. Accordingly, treatment with global RAS antagonists attenuates... (Review)
Review
Inappropriate activation of the renin-angiotensin system (RAS) exacerbates renal and vascular injury. Accordingly, treatment with global RAS antagonists attenuates cardiovascular risk and slows the progression of proteinuric kidney disease. By reducing BP, RAS inhibitors limit secondary immune activation responding to hemodynamic injury in the target organ. However, RAS activation in hematopoietic cells has immunologic effects that diverge from those of RAS stimulation in the kidney and vasculature. In preclinical studies, activating type 1 angiotensin (AT) receptors in T lymphocytes and myeloid cells blunts the polarization of these cells toward proinflammatory phenotypes, protecting the kidney from hypertensive injury and fibrosis. These endogenous functions of immune AT receptors temper the pathogenic actions of renal and vascular AT receptors during hypertension. By counteracting the effects of AT receptor stimulation in the target organ, exogenous administration of AT receptor agonists or angiotensin 1-7 analogs may similarly limit inflammatory injury to the heart and kidney. Moreover, although angiotensin II is the classic effector molecule of the RAS, several RAS enzymes affect immune homeostasis independently of canonic angiotensin II generation. Thus, as reviewed here, multiple components of the RAS signaling cascade influence inflammatory cell phenotype and function with unpredictable and context-specific effects on innate and adaptive immunity.
Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Animals; Humans; Peptide Fragments; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System
PubMed: 28151411
DOI: 10.1681/ASN.2016101066 -
Journal of Clinical Laboratory Analysis May 2024The interference can be a significant source of laboratory errors with the potential to cause immunoassay results to drift. Therefore, we evaluated the interference in...
BACKGROUND
The interference can be a significant source of laboratory errors with the potential to cause immunoassay results to drift. Therefore, we evaluated the interference in various endogenous and exogenous substances on immunoassay for angiotensin I (Ang I), angiotensin II (Ang II), aldosterone, and renin in vitro.
METHODS
Ten endogenous and eight exogenous substances were evaluated at supraphysiologic or supratherapeutic plasma levels using the screening study to identify potential interfering substances. Subsequently, potential interfering substances were further tested within maximum pathological or therapeutic plasma concentration ranges using the dose-response study to determine whether the interference has a significant bias. According to preset acceptance criteria, the interference in potential interfering substances for Ang I, Ang II, and renin and aldosterone assays was determined.
RESULTS
Six potential interfering substances for Ang I immunoassays were identified, namely valsartan, nifedipine, spironolactone, cholesterol, hemoglobin, and triglyceride. Meanwhile, ethanol, nifedipine, spironolactone, heparin sodium, warfarin, hemoglobin, uric acid, cholesterol, and triglyceride appeared to have potential interference in the Ang II assay. Three identified as possible interferents for aldosterone immunoassays were glucose, valsartan, and spironolactone. Moreover, warfarin, valsartan, spironolactone, uric acid, cholesterol, bilirubin unconjugated, triglyceride, and hemoglobin were potential interfering substances for renin immunoassays. However, only spironolactone of these potential interfering substances exceeded preset mean bias limits (less than ±10.0%) in aldosterone immunoassays.
CONCLUSION
Exogenous spironolactone caused clinically significant interference in aldosterone immunoassays. Moreover, the interference in other substances was acceptable in Ang I, Ang II, and renin and aldosterone immunoassays.
Topics: Humans; Angiotensin II; Aldosterone; Renin; Immunoassay; Angiotensin I; Luminescent Measurements
PubMed: 38822626
DOI: 10.1002/jcla.25045 -
Molecular and Cellular Endocrinology Jun 2021Pregnancy demands major cardiovascular, renal and endocrine changes to provide an adequate blood supply for the growing fetus. The renin-angiotensin-aldosterone system... (Review)
Review
Pregnancy demands major cardiovascular, renal and endocrine changes to provide an adequate blood supply for the growing fetus. The renin-angiotensin-aldosterone system plays a key role in this adaptation process. One of its components, prorenin, is released in significant amounts from the ovary and uteroplacental unit. This review describes the sources of prorenin in the periconception period and in pregnancy, including its modulation by in-vitro fertilization protocols, and discusses its potential effects, among others focusing on preeclampsia. It ends with discussing the long-term consequences, even in later life, of inappropriate renin-angiotensin-aldosterone system activity in pregnancy and offers directions for future research. Ultimately, a full understanding of the role of prorenin periconceptionally and during pregnancy will help to develop tools to diagnose and/or prevent reproductive complications.
Topics: Angiotensin I; Angiotensinogen; Female; Fertilization in Vitro; Gene Expression Regulation; Humans; Ovary; Placenta; Pre-Eclampsia; Pregnancy; Renin; Renin-Angiotensin System; Signal Transduction; Uterus
PubMed: 33878417
DOI: 10.1016/j.mce.2021.111281