Effects of irbesartan on gene expression revealed by transcriptome analysis of left atrial tissue in a porcine model of acute rapid pacing in vivo

Chilukoti, Ravi Kumar; Mostertz, Jörg; Bukowska, Alicja; Aderkast, Christoph; Felix, Stephan B.; Busch, M.; Völker, Uwe; Goette, Andreas; Wolke, Carmen; Homuth, Georg; Lendeckel, Uwe

doi:10.1016/j.ijcard.2013.01.007

Cited by 27 publications

(21 citation statements)

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“…NFκB regulated proteins include connective tissue growth factor (CTGF), which contributes to cardiac fibrosis [43], renal proteinuria and failure [101], as well as skin aging [102] following mineralocorticoid excess. SGK1 is further involved in angiotensin II-induced cardiac CTGF formation and fibrosis [103, 104], in cardiac remodelling following increased afterload [7, 105, 106] and in augmentation of fibronectin formation at excessive extracellular glucose concentrations [7]. …”

Section: Sgk1 Sensitive Infammation and Fbrosismentioning

confidence: 99%

Two Liters a Day Keep the Doctor Away? Considerations on the Pathophysiology of Suboptimal Fluid Intake in the Common Population

Läng

Guelinckx

Lemetais

et al. 2017

Kidney Blood Press Res

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Suboptimal fluid intake may require enhanced release of antidiuretic hormone (ADH) or vasopressin for the maintenance of adequate hydration. Enhanced copeptin levels (reflecting enhanced vasopressin levels) in 25% of the common population are associated with enhanced risk of metabolic syndrome with abdominal obesity, type 2 diabetes, hypertension, coronary artery disease, heart failure, vascular dementia, cognitive impairment, microalbuminuria, chronic kidney disease, inflammatory bowel disease, cancer, and premature mortality. Vasopressin stimulates the release of glucocorticoids which in turn up-regulate the serum- and glucocorticoid-inducible kinase 1 (SGK1). Moreover, dehydration upregulates the transcription factor NFAT5, which in turn stimulates SGK1 expression. SGK1 is activated by insulin, growth factors and oxidative stress via phosphatidylinositide-3-kinase, 3-phosphoinositide-dependent kinase PDK1 and mTOR. SGK1 is a powerful stimulator of Na⁺/K⁺-ATPase, carriers (e.g. the Na⁺,K⁺,2Cl^- cotransporter NKCC, the NaCl cotransporter NCC, the Na⁺/H⁺ exchanger NHE3, and the Na⁺ coupled glucose transporter SGLT1), and ion channels (e.g. the epithelial Na⁺ channel ENaC, the Ca²⁺ release activated Ca²⁺ channel Orai1 with its stimulator STIM1, and diverse K⁺ channels). SGK1 further participates in the regulation of the transcription factors nuclear factor kappa-B NFκB, p53, cAMP responsive element binding protein (CREB), activator protein-1, and forkhead transcription factor FKHR-L1 (FOXO3a). Enhanced SGK1 activity fosters the development of hypertension, obesity, diabetes, thrombosis, stroke, inflammation including inflammatory bowel disease and autoimmune disease, cardiac fibrosis, proteinuria, renal failure as well as tumor growth. The present brief review makes the case that suboptimal fluid intake in the common population may enhance vasopressin and glucocorticoid levels thus up-regulating SGK1 expression and favouring the development of SGK1 related pathologies.

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Section: Sgk1 Sensitive Infammation and Fbrosismentioning

confidence: 99%

Two Liters a Day Keep the Doctor Away? Considerations on the Pathophysiology of Suboptimal Fluid Intake in the Common Population

Läng

Guelinckx

Lemetais

et al. 2017

Kidney Blood Press Res

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“…SGK1-dependent expression of CTGF contributes to the mineralocorticoid stimulation of cardiac fibrosis [46,51] and aging of the skin [62]. SGK1 is further involved in angiotensin II-induced cardiac CTGF formation and fibrosis [63,64] as well as in cardiac remodeling following increased afterload [45,65,66]. …”

Section: Role Of Sgk1 In Mineralocorticoid-sensitive Inflammation Andmentioning

confidence: 99%

Mineralocorticoid and SGK1-Sensitive Inflammation and Tissue Fibrosis

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2014

Nephron Physiol

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Effects of mineralocorticoids are not restricted to regulation of epithelial salt transport, extracellular volume and blood pressure; mineralocorticoids also influence a wide variety of seemingly unrelated functions such as inflammation and fibrosis. The present brief review addresses the role of mineralocorticoids in the orchestration of these latter processes. Mineralocorticoids foster inflammation as well as vascular, cardiac, renal and peritoneal fibrosis. Mechanisms involved in mineralocorticoid-sensitive inflammation and fibrosis include the serum- and glucocorticoid-inducible kinase 1 (SGK1), which is genomically upregulated by mineralocorticoids and transforming growth factor β (TGF-β), and stimulated by mineralocorticoid-sensitive phosphatidylinositide 3-kinase. SGK1 upregulates the inflammatory transcription factor nuclear factor-κB, which in turn stimulates the expression of diverse inflammatory mediators including connective tissue growth factor. Moreover, SGK1 inhibits the degradation of the TGF-β-dependent transcription factors Smad2/3. Mineralocorticoids foster the development of T_H17 cells, which is compromised following SGK1 deletion. Excessive SGK1 expression is observed in a wide variety of fibrosing diseases including lung fibrosis, diabetic nephropathy, glomerulonephritis, obstructive kidney disease, experimental nephrotic syndrome, obstructive nephropathy, liver cirrhosis, fibrosing pancreatitis, peritoneal fibrosis, Crohn's disease and celiac disease. The untoward inflammatory and fibrosing effects of mineralocorticoids could be blunted or even reversed by mineralocorticoid receptor blockers, which may thus be considered in the treatment of inflammatory and/or fibrosing disease.

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“…For experiments to investigate the influence of interleukin (IL)-1β (PAN-Biotech GmbH, Aidenbach, Germany) and angiotensin (1-7; Bachem Distribution Services GmbH, Weilam Rhein, Germany), the cells were seeded at a density of 5x10 5 cells/well in a six-well plate (Sarstedt, Nümbrecht, Germany) at a final volume of 3 ml and incubated for 24 h. RNA was prepared using innuPrep RNA Mini kit (Analytik Jena AG, Jena, Germany) according to the manufacturer's instructions. cDNA-synthesis and qPCR were performed exactly as described previously (31). The quantities of mRNA were normalized to α-tubulin mRNA.…”

Section: Rna Preparation and Quantitative Polymerase Chain Reaction (mentioning

confidence: 99%

Expression and function of the ACE2/angiotensin(1–7)/Mas axis in osteosarcoma cell lines U-2 OS and MNNG-HOS

Ender

Dallmer

Lässig

et al. 2014

Molecular Medicine Reports

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The renin-angiotensin-system (RAS), via its classical angiotensin-converting enzyme (ACE)/angiotensin II/angiotensin II type 1 receptor (AT1R)-axis, is associated with proliferation and metastasis of numerous types of solid tumor. AT1R blockers reduce tumor volume and decrease liver and lung metastasis in murine models of osteosarcoma. Expression and function of the alternative ACE2/Ang(1-7)/Mas axis in osteosarcoma is yet to be studied. In the present study, the basic and interleukin (IL)-1β-stimulated expression of components of this alternative RAS axis were analyzed and the impact of Mas on proliferation and/or migration of U-2 OS and MNNG-HOS osteosarcoma cells was studied. Quantitative polymerase chain reaction revealed that the two cell lines expressed the Ang(1‑7)-generating peptidases ACE2, neutral endopeptidase 24.11 and prolyl-endopeptidase together with the putative receptor for Ang(1-7), Mas. IL-1β provoked an induction of Mas mRNA and protein expression which was associated with a reduction of proliferation and migration. By contrast, small interfering RNA-mediated knockdown of Mas expression led to increased cell proliferation. In conclusion, osteosarcoma cells express a functional active alternative ACE2/Ang(1-7)/Mas axis. The induction and reinforcement of this axis may be beneficial for the treatment of osteosarcoma by reducing growth and preventing cancer metastasis. These effects may be achieved directly by the administration of Mas agonists or, indirectly, via blocking the classical AngII RAS axis via ACE inhibitors or AT1R antagonists.

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Effects of irbesartan on gene expression revealed by transcriptome analysis of left atrial tissue in a porcine model of acute rapid pacing in vivo

Cited by 27 publications

References 70 publications

Two Liters a Day Keep the Doctor Away? Considerations on the Pathophysiology of Suboptimal Fluid Intake in the Common Population

Two Liters a Day Keep the Doctor Away? Considerations on the Pathophysiology of Suboptimal Fluid Intake in the Common Population

Mineralocorticoid and SGK1-Sensitive Inflammation and Tissue Fibrosis

Expression and function of the ACE2/angiotensin(1–7)/Mas axis in osteosarcoma cell lines U-2 OS and MNNG-HOS

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