scholarly journals The Network of Angiotensin Receptors in Breast Cancer

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1336
Author(s):  
Filippo Acconcia
Keyword(s):  
Breast Cancer ◽  
Angiotensin Ii ◽  
Current Knowledge ◽  
Molecular System ◽  
Endocrine System ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Transmembrane Receptors ◽  
System Physiology ◽  
Breast Breast Cancer

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.

Androgens augment proximal tubule transport

2004 ◽  
Vol 287 (3) ◽  
pp. F452-F459 ◽  
Author(s):  
Albert Quan ◽  
Sumana Chakravarty ◽  
Jian-Kang Chen ◽  
Jian-Chun Chen ◽  
Samer Loleh ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Specific Binding ◽  
Extracellular Volume ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin

The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min−1·mm−1, P < 0.01). Luminally perfusing with either enalaprilat (10−4 M) to inhibit production of angiotensin II or losartan (10−8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.

Higher Angiotensin II type 1 receptor (AT1R) levels and activity in the post-mortem brains of older persons with Alzheimer's disease

2021 ◽  
Author(s):  
Caglar Cosarderelioglu ◽  
Lolita S Nidadavolu ◽  
Claudene J George ◽  
Ruth Marx ◽  
Laura Powell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Amyloid Β ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Post Mortem ◽  
Protein Levels ◽  
Normal Individuals ◽  
Markers Of Oxidative Stress

Abstract Aging is a key risk factor in Alzheimer's dementia (AD) development and progression. The primary dementia-protective benefits of Angiotensin II subtype 1 receptor (AT1R) blockers are believed to arise from systemic effects on blood pressure. However, a brain-specific renin-angiotensin system (b-RAS) exists, which can be altered by AT1R blockers. Brain RAS acts mainly through three angiotensin receptors: AT1R, AT2R, and AT4R. Changes in these brain angiotensin receptors may accelerate the progression of AD. Using post-mortem frontal cortex brain samples of age- and sex-matched cognitively normal individuals (n = 30) and AD patients (n = 30), we sought to dissect the b-RAS changes associated with AD and assess how these changes correlate with brain markers of oxidative stress, inflammation, and mitochondrial dysfunction as well as amyloid-β and paired helical filament tau pathologies. Our results show higher protein levels of the pro-inflammatory AT1R and phospho-ERK (pERK) in the brains of AD participants. Brain AT1R levels and pERK correlated with higher oxidative stress, lower cognitive performance, and higher tangle and amyloid-β scores. This study identifies molecular changes in b-RAS and offers insight into the role of b-RAS in AD-related brain pathology.

scholarly journals The role of angiotensin II in the regulation of breast cancer cell adhesion and invasion

2006 ◽  
Vol 13 (3) ◽  
pp. 895-903 ◽  
Author(s):  
J R Puddefoot ◽  
U K I Udeozo ◽  
S Barker ◽  
G P Vinson
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Angiotensin Ii ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Renin Angiotensin System ◽  
Adhesion And Invasion

As breast cancer remains the most common cause of cancer death in women, there is a continuing need not only to further characterise the processes of cancer progression, but also to improve accuracy of prognostic markers. Breast epithelial cells express components of the renin angiotensin system and studies suggest that these may be altered in disease progression. In addition, altered integrin expression correlates with lymph node metastasis. The aim of this study was to investigate the relationship between angiotensin II (AII) and integrins in breast tissue and, in particular, their role in breast cancer cell metastasis. Using in vitro assays, AII (10−6 M)-treated MCF-7 and T47D breast cancer cells both show reduced adhesion to extracellular matrix proteins collagen-, fibronectin- and laminin-coated wells (P<0.001) and reduced invasion through collagen-, fibronectin- and laminin-coated membranes (P<0.05). This action was inhibited by co-treatment with the angiotensin type 1 receptor (AT1R) antagonist losartan (10−5 M). The addition of the AT2R inhibitor PD123319 (10−5 M) to AII-treated cells had no significant effect. Semi-quantitative reverse transcriptase-PCR and western blotting revealed that cells treated with AII (10−6 M) expressed lower levels of both integrin α3 and β1. Using specific inhibitors, this was shown to occur through protein kinase C signalling. These data suggest that AII reduces cell adhesion and invasion through the type 1 receptor and that this effect may be due to reduced expression of integrins, and in particular α3 and β1.

scholarly journals Angiotensin-(1-7): Translational Avenues in Cardiovascular Control

2019 ◽  
Vol 32 (12) ◽  
pp. 1133-1142 ◽  
Author(s):  
Daniela Medina ◽  
Amy C Arnold
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Current Knowledge ◽  
Renin Angiotensin System ◽  
Cardiovascular Control ◽  
Biologically Active ◽  
Global Public Health ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Cardiovascular Actions

Abstract Despite decades of research and numerous treatment approaches, hypertension and cardiovascular disease remain leading global public health problems. A major contributor to regulation of blood pressure, and the development of hypertension, is the renin-angiotensin system. Of particular concern, uncontrolled activation of angiotensin II contributes to hypertension and associated cardiovascular risk, with antihypertensive therapies currently available to block the formation and deleterious actions of this hormone. More recently, angiotensin-(1–7) has emerged as a biologically active intermediate of the vasodilatory arm of the renin-angiotensin system. This hormone antagonizes angiotensin II actions as well as offers antihypertensive, antihypertrophic, antiatherogenic, antiarrhythmogenic, antifibrotic and antithrombotic properties. Angiotensin-(1–7) elicits beneficial cardiovascular actions through mas G protein-coupled receptors, which are found in numerous tissues pivotal to control of blood pressure including the brain, heart, kidneys, and vasculature. Despite accumulating evidence for favorable effects of angiotensin-(1–7) in animal models, there is a paucity of clinical studies and pharmacokinetic limitations, thus limiting the development of therapeutic agents to better understand cardiovascular actions of this vasodilatory peptide hormone in humans. This review highlights current knowledge on the role of angiotensin-(1–7) in cardiovascular control, with an emphasis on significant animal, human, and therapeutic research efforts.

scholarly journals Synthesis and Secretion of Angiotensin II by the Prostate Gland in Vitro

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 392-398 ◽  
Author(s):  
Orla A. O’Mahony ◽  
Stewart Barker ◽  
John R. Puddefoot ◽  
Gavin P. Vinson
Keyword(s):  
Angiotensin Ii ◽  
Seminal Plasma ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Angiotensin Receptors ◽  
Lncap Cells ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Rat Prostate

The renin angiotensin system has been shown to have tissue-related functions that are distinct from its systemic roles. We showed that angiotensin II type 1 (AT1) receptors are present in mammalian sperm, and angiotensin II stimulates sperm motility and capacitation. In addition, angiotensin II is present in human seminal plasma at concentrations higher than found in blood. In testing the possibility that the prostate may be the source of seminal plasma angiotensin II, mRNA coding for angiotensinogen, (pro)renin, and angiotensin-converting enzyme were identified by RT-PCR in rat and human prostate and in prostate LNCaP cells, as well as the angiotensin receptors types 1 and 2 (AT1 and AT2) in human tissues and AT1 in rat. In human tissue, immunocytochemistry showed cellular colocalization of renin with the AT1 receptor in secretory epithelial cells. Confirmation of the capacity of the prostate to secrete angiotensin II was shown by the detection of immunoreactive angiotensin in media removed from rat prostate organ cultures and LNCaP cells. Rat prostate angiotensin secretion was enhanced by dihydrotestosterone, but LNCaP angiotensin was stimulated by estradiol. This stimulation was blocked by tamoxifen. Rat prostate AT1 receptor expression was much greater in prepuberal than in postpuberal rats but was not affected by a low-sodium diet. It was, however, significantly enhanced by captopril pretreatment. These findings all suggest the independence of prostate and systemic renin angiotensin system regulation. The data presented here suggest that the prostate may be a source of the secreted angiotensin II found in seminal plasma.

Angiotensin II responses in AT1A receptor-deficient mice: a role for AT1B receptors in blood pressure regulation

1997 ◽  
Vol 272 (4) ◽  
pp. F515-F520 ◽  
Author(s):  
M. I. Oliverio ◽  
C. F. Best ◽  
H. S. Kim ◽  
W. J. Arendshorst ◽  
O. Smithies ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Blood Pressure Regulation ◽  
Angiotensin Receptors ◽  
Pressure Regulation ◽  
At1 Receptor Antagonists ◽  
At1a Receptor

Most of the classic functions of the renin-angiotensin system are mediated by type 1 (AT1) angiotensin receptors, of which two subtypes, AT1A and AT1B, have been identified. However, distinct functions for these two AT1 receptors have been difficult to separate. We examined the pressor effects of angiotensin II in Agtr1A -/- mice, which lack AT1A receptors. In enalapril-pretreated Agtr1A -/- mice, angiotensin II caused significant and dose-proportional increases in mean arterial pressure. This pressor response was not blocked by pretreatment with sympatholytic agents but was completely inhibited by the AT1-receptor antagonists, losartan and candesartan, suggesting that it is directly mediated by AT1B receptors. Chronic treatment of Agtr1A -/- mice with losartan reduced systolic blood pressure from 80 +/- 5 to 72 +/- 4 mmHg (P < 0.04), suggesting a role for AT1B receptors in chronic blood pressure regulation. These studies provide the first demonstration of in vivo pressor effects mediated by AT1B receptors and demonstrate that, when AT1A receptors are absent, the AT1B receptor contributes to the regulation of resting blood pressure.

Investigating the role of angiotensin II in thirst: Interactions between arterial pressure and the control of drinking

1992 ◽  
Vol 70 (5) ◽  
pp. 791-797 ◽  
Author(s):  
Mark D. Evered
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Current Knowledge ◽  
Physiological Role ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Physiological Variables ◽  
Recent Developments

Several lines of evidence suggest that angiotensin II plays a physiological role in the control of thirst. Establishing that, however, has been surprisingly difficult, given our current knowledge about the renin–angiotensin systems in the circulation and the brain and the variety of techniques available to measure and manipulate them. A major problem is that stimulating or blocking the renin–angiotensin system affects several physiological variables simultaneously. Since several of these variables also influence the controls of water intake directly or indirectly, the interpretation of the effect on drinking becomes more difficult. To illustrate the problem and recent developments, this paper describes some of the interactions between the effects of angiotensin II on arterial pressure and thirst, and it shows how they have contributed to the controversy over the physiological role of the peptide.Key words: renin–angiotensin system, thirst, arterial pressure.

scholarly journals The renin–angiotensin system in the breast and breast cancer

2011 ◽  
Vol 19 (1) ◽  
pp. R1-R19 ◽  
Author(s):  
Gavin P Vinson ◽  
Stewart Barker ◽  
John R Puddefoot
Keyword(s):  
Breast Cancer ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Cell Types ◽  
At1 Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Close Relationship ◽  
And Function ◽  
At2 Receptors

Much evidence now suggests that angiotensin II has roles in normal functions of the breast that may be altered or attenuated in cancer. Both angiotensin type 1 (AT1) and type 2 (AT2) receptors are present particularly in the secretory epithelium. Additionally, all the elements of a tissue renin–angiotensin system, angiotensinogen, prorenin and angiotensin-converting enzyme (ACE), are also present and distributed in different cell types in a manner suggesting a close relationship with sites of angiotensin II activity. These findings are consistent with the concept that stromal elements and myoepithelium are instrumental in maintaining normal epithelial structure and function. In disease, this system becomes disrupted, particularly in invasive carcinoma. Both AT1 and AT2 receptors are present in tumours and may be up-regulated in some. Experimentally, angiotensin II, acting via the AT1 receptor, increases tumour cell proliferation and angiogenesis, both these are inhibited by blocking its production or function. Epidemiological evidence on the effect of expression levels of ACE or the distribution of ACE or AT1 receptor variants in many types of cancer gives indirect support to these concepts. It is possible that there is a case for the therapeutic use of high doses of ACE inhibitors and AT1 receptor blockers in breast cancer, as there may be for AT2 receptor agonists, though this awaits full investigation. Attention is drawn to the possibility of blocking specific AT1-mediated intracellular signalling pathways, for example by AT1-directed antibodies, which exploit the possibility that the extracellular N-terminus of the AT1 receptor may have previously unsuspected signalling roles.

scholarly journals The Impact of microRNAs in Renin–Angiotensin-System-Induced Cardiac Remodelling

2021 ◽  
Vol 22 (9) ◽  
pp. 4762
Author(s):  
Michaela Adamcova ◽  
Ippei Kawano ◽  
Fedor Simko
Keyword(s):  
Angiotensin Ii ◽  
Immune Cell ◽  
Current Knowledge ◽  
Early Stage ◽  
Renin Angiotensin System ◽  
Cardiac Response ◽  
Cardiac Remodelling ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Impact

Current knowledge on the renin–angiotensin system (RAS) indicates its central role in the pathogenesis of cardiovascular remodelling via both hemodynamic alterations and direct growth and the proliferation effects of angiotensin II or aldosterone resulting in the hypertrophy of cardiomyocytes, the proliferation of fibroblasts, and inflammatory immune cell activation. The noncoding regulatory microRNAs has recently emerged as a completely novel approach to the study of the RAS. A growing number of microRNAs serve as mediators and/or regulators of RAS-induced cardiac remodelling by directly targeting RAS enzymes, receptors, signalling molecules, or inhibitors of signalling pathways. Specifically, microRNAs that directly modulate pro-hypertrophic, pro-fibrotic and pro-inflammatory signalling initiated by angiotensin II receptor type 1 (AT1R) stimulation are of particular relevance in mediating the cardiovascular effects of the RAS. The aim of this review is to summarize the current knowledge in the field that is still in the early stage of preclinical investigation with occasionally conflicting reports. Understanding the big picture of microRNAs not only aids in the improved understanding of cardiac response to injury but also leads to better therapeutic strategies utilizing microRNAs as biomarkers, therapeutic agents and pharmacological targets

scholarly journals Angiotensin II and Angiotensin Receptors 1 and 2—Multifunctional System in Cells Biology, What Do We Know?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 381
Author(s):  
Maksymilian Ziaja ◽  
Kinga Anna Urbanek ◽  
Karolina Kowalska ◽  
Agnieszka Wanda Piastowska-Ciesielska
Keyword(s):  
Angiotensin Ii ◽  
Cardiovascular System ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Individual ◽  
In Cells

For years, the renin-angiotensin system (RAS) has been perceived as a system whose role is to primarily modulate the functioning of the cardiovascular system. Years of research into the role of RAS have provided the necessary data to confirm that the role of RAS is very complex and not limited to the cardiovascular system. The presence of individual elements of the renin-angiotensin (RA) system allows to control many processes, ranging from the memorization to pro-cancer processes. Maintaining the proportions between the individual axes of the RA system allows for achieving a balance, often called homeostasis. Thus, any disturbance in the expression or activity of individual RAS elements leads to pathophysiological processes.

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