Effect of extracellular and intracellular angiotensins on heart cell function; on the cardiac renin–angiotensin system

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.

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Role of the Renin Angiotensin System on Bone Marrow‐Derived Stem Cell Function and its Impact on Skeletal Muscle Angiogenesis After Electrical Stimulation

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.1030.10 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Micheline M Resende ◽

Timothy J. Stodola ◽

Andrew S. Greene

Keyword(s):

Skeletal Muscle ◽

Bone Marrow ◽

Stem Cell ◽

Electrical Stimulation ◽

Cell Function ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin

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

Hypertension ◽

10.1161/hypertensionaha.121.18600 ◽

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.

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The tissue renin-angiotensin system in human pancreas

Journal of Endocrinology ◽

10.1677/joe.0.1610317 ◽

1999 ◽

Vol 161 (2) ◽

pp. 317-322 ◽

Cited By ~ 111

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.

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