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Journal of Neuro-oncology May 2018Gliomas are the most common primary intrinsic tumor in the brain and are classified as low- or high-grade according to the World Health Organization (WHO). Patients with... (Review)
Review
Gliomas are the most common primary intrinsic tumor in the brain and are classified as low- or high-grade according to the World Health Organization (WHO). Patients with high-grade gliomas (HGG) who undergo surgical resection with adjuvant therapy have a mean overall survival of 15 months and 100% recurrence. The renin-angiotensin system (RAS), the primary regulator of cardiovascular circulation, exhibits local action and works as a paracrine system. In the context of this local regulation, the expression of RAS peptides and receptors has been detected in different kinds of tumors, including gliomas. The dysregulation of RAS components plays a significant role in the proliferation, angiogenesis, and invasion of these tumors, and therefore in their outcomes. The study and potential application of RAS peptides and receptors as biomarkers in gliomas could bring advantages against the limitations of current tumoral markers and should be considered in the future. The targeting of RAS components by RAS blockers has shown potential of being protective against cancer and improving immunotherapy. In gliomas, RAS blockers have shown a broad spectrum for beneficial effects and are being considered for use in treatment protocols. This review aims to summarize the background behind how RAS plays a role in gliomagenesis and explore the evidence that could lead to their use as biomarkers and treatment adjuvants.
Topics: Angiotensins; Biomarkers; Brain Neoplasms; Glioma; Humans; Peptide Fragments; Renin-Angiotensin System
PubMed: 29450812
DOI: 10.1007/s11060-018-2789-5 -
Endocrine Regulations Jan 2013Although more than 100 years passed from the renin-angiotensin system (RAS) discovery, new knowledge is still ceaselessly accruing in this field. The present review... (Review)
Review
UNLABELLED
Although more than 100 years passed from the renin-angiotensin system (RAS) discovery, new knowledge is still ceaselessly accruing in this field. The present review provides brief overview on the history of the RAS investigation, circulating and tissue RAS, and outlines the physiological functions of the RAS major active substance, angiotensin II (ANG II). Circulating ANG II is generated from angiotensin I (ANG I) by carboxypeptidaze angiotensin-converting enzyme (ACE) expressed in the pulmonary endothelial cells. ANG I is formed from angiotensinogen, originating in the liver, by renal peptidase renin secreted by the juxtaglomerular cells. The ANG II effects are mediated mainly via AT1 receptors. Scientific, medical, and pharmacological interests in the RAS relay mainly in its potency to influence the blood pressure and heart hypertrophy. Inhibition of ACE and AT1 receptors has been shown to be very useful in the hypertension management although several unexpected effects of this treatment led to the initiation of new studies. This review also describes other bioactive angiotensins and modifying enzymes identified during the last years, the ways how the RAS activity can be measured and ANG II degraded in the organism. It also indicates the most convenient models for the RAS investigation. Finally, the major mechanisms of the RAS activity regulation are also described.
KEYWORDS
angiotensin, angiotensin-converting enzyme, angiotensin-converting enzyme 2, angiotensin AT1 receptors, experimental model.
Topics: Angiotensins; Animals; Endocrinology; Humans; Models, Biological; Receptors, Angiotensin; Renin; Renin-Angiotensin System; Tissue Distribution
PubMed: 23363256
DOI: 10.4149/endo_2013_01_39 -
Journal of the... Dec 2005The concept of tissue renin-angiotensin systems (RAS) is now well established and it is now usual to think in terms of renal and tissue systems. At the same time it has... (Review)
Review
The concept of tissue renin-angiotensin systems (RAS) is now well established and it is now usual to think in terms of renal and tissue systems. At the same time it has emerged that angiotensin II (Ang II) is not the only biologically active peptide generated by the RAS. At least three others have been identified: the heptapeptide Ang III, the hexapeptide Ang IV and Ang 1-7. Specific receptors exits for the last two peptides. In addition, the range of possible physiological and pathophysiological properties for Ang II has been expanding. The current perception of the RAS is therefore that of a much more complex system than previously believed, with autocrine, paracrine and endocrine properties extending beyond the cardiovascular system. This mini-review focuses on the synthetic pathways of the Ang peptides and describes some of their pleiotropic actions.
Topics: Aldosterone; Angiotensin II; Angiotensins; Animals; Cardiovascular Physiological Phenomena; Humans; Peptide Fragments; Renin-Angiotensin System
PubMed: 16525942
DOI: 10.3317/jraas.2005.018 -
Pflugers Archiv : European Journal of... Mar 2011With the advancement of medical and investigative science, it is somewhat surprising that although it is possible to stabilise medical patients with hypertension and the... (Review)
Review
With the advancement of medical and investigative science, it is somewhat surprising that although it is possible to stabilise medical patients with hypertension and the associated kidney dysfunction, obesity, diabetes and even cancer, there is still no clear method of significantly reducing these chronic disease pathologies, and thus, extending life expectancy. There is one hormone common to these pathologies, the antagonism of which goes some way to clinical improvements, and this is angiotensin, which is released during hypovolaemia. Angiotensin antagonists are used to treat many of these pathologies, and it has been shown in the obesity literature that angiotensin antagonists decrease weight, but also increase the drinking of water. Increased cellular hydration, and hence, improved mitochondrial metabolism could be one of the mechanisms for the reduction in weight seen in these studies, as well as for reducing the other pathologies, all showing metabolic dysfunction. It appears that the application of straightforward physiological regulation might be an appropriate medical approach to the prevention of hypertension, kidney disease, obesity, diabetes and cancer, and thus, to an increased life expectancy.
Topics: Angiotensins; Diabetes Mellitus; Drinking; Humans; Hypertension; Kidney Diseases; Longevity; Mitochondria; Obesity
PubMed: 21165644
DOI: 10.1007/s00424-010-0911-4 -
Current Pharmaceutical Design 2003The circulating renin-angiotensin system (RAS) has a well-described role in circulatory homeostasis. Recently, local tissue-based RAS have also been described which... (Review)
Review
The circulating renin-angiotensin system (RAS) has a well-described role in circulatory homeostasis. Recently, local tissue-based RAS have also been described which appear to play a key role in the injury/repair response. The expression of RAS components and the elevation of angiotensin converting enzyme in a number of interstitial lung diseases suggests the existence of a pulmonary RAS and that angiotensin II could mediate, at least in part, the response to lung injury. Activation of a local RAS within the pulmonary circulation and lung parenchyma could influence the pathogenesis of lung injury via a number of mechanisms including an increase in vascular permeability, vascular tone and fibroblast activity, and by reducing alveolar epithelial cell survival. The ability of both ACE inhibitors and angiotensin II receptor antagonists to attenuate experimental lung injury further supports a role for RAS activation and suggests these agents may be useful in the treatment of diffuse parenchymal lung disease. However, further studies are required to delineate the cell types responsible for RAS component expression in the lung and also to identify the key effector molecules of this system. The presence of common polymorphisms in RAS genes and their study in relation to specific physiological phenotypes will aid both our understanding of the role of RAS in the lung and also aid the targeting of future therapies.
Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Humans; Lung; Renin-Angiotensin System
PubMed: 12570789
DOI: 10.2174/1381612033455431 -
Scientific American Mar 1959
Topics: Angiotensins
PubMed: 13635038
DOI: 10.1038/scientificamerican0359-54 -
Hypertension (Dallas, Tex. : 1979) Nov 1991We provide a new foundation for an alternative interpretation of the biochemical physiology of the brain and other tissue angiotensin systems on the basis of research... (Review)
Review
We provide a new foundation for an alternative interpretation of the biochemical physiology of the brain and other tissue angiotensin systems on the basis of research done in our laboratory. This perspective is prompted by the discovery that angiotensin-(1-7) has cellular functions that differ from those established for angiotensin II. Although angiotensin-(1-7) is not an agonist in terms of activating vasoconstriction, stimulating thirst, or promoting aldosterone release, the heptapeptide caused neuronal excitation and vasopressin release with a potency similar to that found with angiotensin II. Furthermore, angiotensin-(1-7) enhances the production of prostanoids by a receptor-mediated event that causes no associated rise in intracellular Ca2+. These actions of angiotensin-(1-7) provide a new understanding of the heterogeneous functions of angiotensin peptides as modulators of a wide range of regulatory functions in mammals.
Topics: Angiotensin I; Angiotensin II; Angiotensinogen; Angiotensins; Animals; Biotransformation; Humans; Peptide Fragments; RNA, Messenger; Renin
PubMed: 1937675
DOI: 10.1161/01.hyp.18.5_suppl.iii126 -
Peptides Oct 2009Two research groups in both North and South America independently discovered that renin released a novel vasopressor agent. The Argentine group named it hypertensin, and... (Review)
Review
Two research groups in both North and South America independently discovered that renin released a novel vasopressor agent. The Argentine group named it hypertensin, and called its plasma protein substrate hypertensinogen. The group from the United States named it angiotonin. In 1958, Braun Menendez and Irvine Page suggested that the peptide should be named angiotensin. The combined name eventually became commonly used to avoid linguistic confusion. Research scientists and physicians today acknowledge that studies of the renin-angiotensin system (RAS) have greatly improved our understanding of several diseases. Certainly, medical practice profited significantly from the synthesis and application of numerous pharmacological agents that antagonize either the biosynthesis or pharmacological responses of endogenously generated angiotensin II. Ultimately, discovery of the renin-angiotensin system led to many studies that resulted in therapies for vascular disease. This article briefly reviews research related to the discovery of angiotensin and indicates the importance of additional studies related to the RAS.
Topics: Amino Acid Sequence; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Argentina; Blood Pressure; History, 20th Century; History, 21st Century; Humans; Hypertension; Molecular Sequence Data; Renin-Angiotensin System; Research Personnel; United States
PubMed: 19595728
DOI: 10.1016/j.peptides.2009.07.003 -
Biologica Latina 1964
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Annales Pharmaceutiques Francaises Mar 2005The renin-angiotensin system (RAS) is a major physiological regulator of vascular tone and is implicated in cardiovascular pathophysiology. More recently, basic research... (Review)
Review
The renin-angiotensin system (RAS) is a major physiological regulator of vascular tone and is implicated in cardiovascular pathophysiology. More recently, basic research has however continuously extended our understanding of the complexicity of the systemic and tissular RASs. The peptid hormone, angiotensin II, acts primarily via type I (AT1) and type II (AT2) angiotensin receptors. Most, if not all, of the peripheral and central actions of angiotensin II, including vasoconstriction, renal salt and water retention, facilitation of sympathetic transmission, modification of vascular and cardiac structure, oxydative stress stimulation and proinflammatory action were all thought to be mediated by the angiotensin type 1 receptor, AT1. Angiotensin II/III exerts actions through the AT2 receptor, which are directly opposed to those mediated by the AT1 receptor. Most notably, proteolytic fragments of angiotensin II also have biological activity via ther own receptors: angiotensin-(1-7)/AT1-7 and angiotensin IV/AT4. They are vasodilators in many arterial beds. The identification of these angiotensins opens the way to develop new therapeutics.
Topics: Angiotensins; Humans; Receptors, Angiotensin; Renin; Renin-Angiotensin System
PubMed: 15976682
DOI: 10.1016/s0003-4509(05)82265-5