scholarly journals The tissue renin-angiotensin system in human pancreas

1999 ◽  
Vol 161 (2) ◽  
pp. 317-322 ◽  
Author(s):  
M Tahmasebi ◽  
ER Inwang ◽  
GP Vinson ◽  
Keyword(s):  
Islets Of Langerhans ◽  
Cell Function ◽  
In Situ Hybridisation ◽  
Renin Angiotensin System ◽  
Cell Types ◽  
Human Pancreas ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Glucagon And Insulin ◽  
Sites Of Action

Evidence exists for the presence of a discrete tissue renin-angiotensin system (RAS) in mouse and rat pancreas that is thought largely to be associated with the vasculature. To investigate this in the human pancreas, and to establish whether the cellular sites of RAS components include the islets of Langerhans, we used immunocytochemistry to localise the expression of angiotensin II (AT1) receptors and (pro)renin, and non-isotopic in situ hybridisation to localise transcription of the (pro)renin gene. Identification of cell types in the islets of Langerhans was achieved using antibodies to glucagon and insulin. The results show the presence of the AT1 receptor and (pro)renin both in the beta cells of the islets of Langerhans, and in endothelial cells of the pancreatic vasculature. Transcription of (pro)renin mRNA, however, was confined to connective tissue surrounding the blood vessels and in reticular fibres within the islets. These findings are similar to those obtained in other tissues, and suggest that renin may be released from its sites of synthesis and taken up by possible cellular sites of action. The results presented here suggest that a tissue RAS may be present in human pancreas and that it may directly affect beta cell function as well as pancreatic blood flow.

scholarly journals Regulation and expression of a renin-angiotensin system in human pancreas and pancreatic endocrine tumours

2002 ◽  
pp. 567-572 ◽  
Author(s):  
KY Lam ◽  
PS Leung
Keyword(s):  
Renin Angiotensin System ◽  
Receptor Protein ◽  
Pancreatic Ducts ◽  
Human Pancreas ◽  
Rt Pcr ◽  
Angiotensin System ◽  
Endocrine Tumours ◽  
Renin Angiotensin ◽  
Objective Evidence ◽  
Pancreatic Endocrine Tumours

OBJECTIVE: Evidence exists for the presence of a renin-angiotensin system (RAS) in the pancreas. The aims of this study were to prove the presence of an intrinsic RAS in the human pancreas and to analyse the role of such an RAS in pancreatic endocrine tumours (PETs). METHODS: Gene expression of key RAS components (angiotensinogen and angiotensin II receptors, namely AT1 and AT2) was investigated in human pancreas and in PETs by semi-quantitative RT-PCR and immunohistochemistry. RESULTS: Expression of mRNAs of RAS components was found in human pancreas and in PETs. Data from semi-quantitative RT-PCR analysis demonstrated an increase in the mRNA expression of angiotensinogen and AT2 receptor in PETs when compared with that in normal pancreas. By immunohistochemistry, angiotensinogen protein was predominantly localized in the pancreatic islets while AT1 receptor protein was in the pancreatic ducts. CONCLUSIONS: The data support the notion of the existence of an intrinsic RAS in the human pancreas. It also indicates, for the first time, that such a local pancreatic RAS is subject to regulation by PETs and its significant change may have pathophysiological relevance in patients with PETs.

scholarly journals The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome

2012 ◽  
Vol 302 (6) ◽  
pp. H1219-H1230 ◽  
Author(s):  
Kelly Putnam ◽  
Robin Shoemaker ◽  
Frederique Yiannikouris ◽  
Lisa A. Cassis
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Cell Types ◽  
The United States ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Metabolic Syndrome ◽  
Altered Glucose

The renin-angiotensin system (RAS) is an important therapeutic target in the treatment of hypertension. Obesity has emerged as a primary contributor to essential hypertension in the United States and clusters with other metabolic disorders (hyperglycemia, hypertension, high triglycerides, low HDL cholesterol) defined within the metabolic syndrome. In addition to hypertension, RAS blockade may also serve as an effective treatment strategy to control impaired glucose and insulin tolerance and dyslipidemias in patients with the metabolic syndrome. Hyperglycemia, insulin resistance, and/or specific cholesterol metabolites have been demonstrated to activate components required for the synthesis [angiotensinogen, renin, angiotensin-converting enzyme (ACE)], degradation (ACE2), or responsiveness (angiotensin II type 1 receptors, Mas receptors) to angiotensin peptides in cell types (e.g., pancreatic islet cells, adipocytes, macrophages) that mediate specific disorders of the metabolic syndrome. An activated local RAS in these cell types may contribute to dysregulated function by promoting oxidative stress, apoptosis, and inflammation. This review will discuss data demonstrating the regulation of components of the RAS by cholesterol and its metabolites, glucose, and/or insulin in cell types implicated in disorders of the metabolic syndrome. In addition, we discuss data supporting a role for an activated local RAS in dyslipidemias and glucose intolerance/insulin resistance and the development of hypertension in the metabolic syndrome. Identification of an activated RAS as a common thread contributing to several disorders of the metabolic syndrome makes the use of angiotensin receptor blockers and ACE inhibitors an intriguing and novel option for multisymptom treatment.

scholarly journals Role of the renin angiotensin system on bone marrow-derived stem cell function and its impact on skeletal muscle angiogenesis

2010 ◽  
Vol 42 (3) ◽  
pp. 437-444 ◽  
Author(s):  
Micheline M. de Resende ◽  
Timothy J. Stodola ◽  
Andrew S. Greene
Keyword(s):  
Skeletal Muscle ◽  
Bone Marrow ◽  
Endothelial Cell ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Renin Angiotensin System ◽  
Brown Norway ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

Autologous bone marrow cell (BMC) transplantation has been shown as a potential approach to treat various ischemic diseases. However, under many conditions BMC dysfunction has been reported, leading to poor cell engraftment and a failure of tissue revascularization. We have previously shown that skeletal muscle angiogenesis induced by electrical stimulation (ES) is impaired in the SS/Mcwi rats and that this effect is related to a dysregulation of the renin angiotensin system (RAS) that is normalized by the replacement of chromosome 13 derived from the Brown Norway rat (SS-13BN/Mcwi consomic rats). The present study explored bone marrow-derived endothelial cell (BM-EC) function in the SS/Mcwi rat and its impact on skeletal muscle angiogenesis induced by ES. SS/Mcwi rats were randomized to receive BMC from: SS/Mcwi; SS-13BN/Mcwi; SS/Mcwi rats infused with saline or ANG II (3 ng·kg−1·min−1). BMC were injected in the stimulated tibialis anterior muscle of SS/Mcwi rats. Vessel density was evaluated in unstimulated and stimulated muscles after 7 days of ES. BMC isolated from SS/Mcwi or SS/Mcwi rats infused with saline failed to restore angiogenesis induced by ES. However, BMC isolated from SS-13BN/Mcwi and SS/Mcwi rats infused with ANG II effectively restored the angiogenesis response in the SS/Mcwi recipient. Furthermore, ANG II infusion increased the capacity of BM-EC to induce endothelial cell tube formation in vitro and slightly increased VEGF protein expression. This study suggests that dysregulation of the RAS in the SS/Mcwi rat contributes to impaired BM-EC function and could impact the angiogenic therapeutic potential of BMC.

scholarly journals Comparative Studies of Renin-Null Zebrafish and Mice Provide New Functional Insights

Hypertension ◽  
2022 ◽  
Author(s):  
Scott Hoffmann ◽  
Linda Mullins ◽  
Sebastien Rider ◽  
Cara Brown ◽  
Charlotte B. Buckley ◽  
...  
Keyword(s):  
Cell Function ◽  
Smooth Muscle Actin ◽  
Larval Growth ◽  
Renin Angiotensin System ◽  
Sequencing Analysis ◽  
Renal Vasculature ◽  
Exon 2 ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Larval Stages

Background: The renin-angiotensin system is highly conserved across vertebrates, including zebrafish, which possess orthologous genes coding for renin-angiotensin system proteins, and specialized mural cells of the kidney arterioles, capable of synthesising and secreting renin. Methods: We generated zebrafish with CRISPR-Cas9-targeted knockout of renin ( ren −/− ) to investigate renin function in a low blood pressure environment. We used single-cell (10×) RNA sequencing analysis to compare the transcriptome profiles of renin lineage cells from mesonephric kidneys of ren −/− with ren +/+ zebrafish and with the metanephric kidneys of Ren1 c−/− and Ren1 c +/+ mice. Results: The ren −/− larvae exhibited delays in larval growth, glomerular fusion and appearance of a swim bladder, but were viable and withstood low salinity during early larval stages. Optogenetic ablation of renin-expressing cells, located at the anterior mesenteric artery of 3-day-old larvae, caused a loss of tone, due to diminished contractility. The ren −/− mesonephric kidney exhibited vacuolated cells in the proximal tubule, which were also observed in Ren1 c−/− mouse kidney. Fluorescent reporters for renin and smooth muscle actin ( tg(ren:LifeAct-RFP; acta2:EGFP )), revealed a dramatic recruitment of renin lineage cells along the renal vasculature of adult ren −/− fish, suggesting a continued requirement for renin, in the absence of detectable angiotensin metabolites, as seen in the Ren1 YFP Ren1 c−/− mouse. Both phenotypes were rescued by alleles lacking the potential for glycosylation at exon 2, suggesting that glycosylation is not essential for normal physiological function. Conclusions: Phenotypic similarities and transcriptional variations between mouse and zebrafish renin knockouts suggests evolution of renin cell function with terrestrial survival.

scholarly journals Cell-Type-Specific Expression of Renin-Angiotensin-System Components in the Human Body and Its Relevance to SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Hemant Suryawanshi ◽  
Pavel Morozov ◽  
Thangamani Muthukumar ◽  
Benjamin R. tenOever ◽  
Masashi Yamaji ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Cell Types ◽  
The Body ◽  
Cell Type ◽  
Specific Expression ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Viral Interference ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

AbstractWe have analyzed the cell-type-specific expression of the renin-angiotensin system (RAS) components across 141 cell types or subtypes as defined by single-cell RNA-seq (scRNA-seq) analysis. ACE2, one of the components of RAS, also facilitates SARS-CoV-2 entry into cells in cooperation with its associated protease TMPRSS2. Therefore, our analysis also contributes to the understanding of SARS-CoV-2 infection, spreading of the virus throughout the body, and potential viral interference with RAS in COVID-19 patients.

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.

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