scholarly journals (Pro)renin Receptor Expression Increases throughout the Colorectal Adenoma—Adenocarcinoma Sequence and It Is Associated with Worse Colorectal Cancer Prognosis

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 881 ◽  
Author(s):  
Maider Beitia ◽  
Jon Danel Solano-Iturri ◽  
Peio Errarte ◽  
Julio Calvete-Candenas ◽  
Alberto Loizate ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Renin Angiotensin System ◽  
Distant Metastases ◽  
Receptor Expression ◽  
Cancer Prognosis ◽  
Angiotensin System ◽  
Local Tumour ◽  
Potential Use

(Pro)renin receptor (PRR) is a protein that takes part in several signaling pathways such as Renin Angiotensin System and Wnt signalling. Its biological role has recently been related to cancer progression and in this study, we investigated its relevance in colorectal cancer (CRC). To that end, we analysed the immunohistochemical expression of PRR in adenomatous polyps and CRCs from the same patients (n = 42), and in primary tumours and nodal and liver metastases from advanced CRC patients (n = 294). In addition, the soluble fraction of PRR was measured by ELISA in plasma samples from 161 CRC patients. The results showed that PRR expression was gradually augmented along the uninvolved mucosa–adenoma–adenocarcinoma sequence. Besides, the stronger expression of PRR in primary tumours was markedly associated with local tumour extent and the onset of metastases. Moreover, PRR expression in both primary and distant metastases was associated with worse 5- and 10-year survival of CRC patients. Plasmatic PRR levels did not change with respect to controls and were not associated with CRC aggressiveness. These results suggest a key role of PRR in the development and progression of CRC and a potential use of this protein as a new prognostic biomarker and/or therapeutic target for this disease.

scholarly journals Cardiac-specific suppression of NF-κB signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system

2014 ◽  
Vol 307 (7) ◽  
pp. H1036-H1045 ◽  
Author(s):  
Candice M. Thomas ◽  
Qian Chen Yong ◽  
Rodolfo M. Rosa ◽  
Rachid Seqqat ◽  
Shanthi Gopal ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Heart Function ◽  
Renin Angiotensin System ◽  
Receptor Expression ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Transgenic Mouse Line ◽  
Plasmic Reticulum ◽  
Nondiabetic Control

Activation of NF-κB signaling in the heart may be protective or deleterious depending on the pathological context. In diabetes, the role of NF-κB in cardiac dysfunction has been investigated using pharmacological approaches that have a limitation of being nonspecific. Furthermore, the specific cellular pathways by which NF-κB modulates heart function in diabetes have not been identified. To address these questions, we used a transgenic mouse line expressing mutated IκB-α in the heart (3M mice), which prevented activation of canonical NF-κB signaling. Diabetes was developed by streptozotocin injections in wild-type (WT) and 3M mice. Diabetic WT mice developed systolic and diastolic cardiac dysfunction by the 12th week, as measured by echocardiography. In contrast, cardiac function was preserved in 3M mice up to 24 wk of diabetes. Diabetes induced an elevation in cardiac oxidative stress in diabetic WT mice but not 3M mice compared with nondiabetic control mice. In diabetic WT mice, an increase in the phospholamban/sarco(endo)plasmic reticulum Ca2+-ATPase 2 ratio and decrease in ryanodine receptor expression were observed, whereas diabetic 3M mice showed an opposite effect on these parameters of Ca2+ handling. Significantly, renin-angiotensin system activity was suppressed in diabetic 3M mice compared with an increase in WT animals. In conclusion, these results demonstrate that inhibition of NF-κB signaling in the heart prevents diabetes-induced cardiac dysfunction through preserved Ca2+ handling and inhibition of the cardiac renin-angiotensin system.

Oryeongsan (Wulingsan) Ameliorates Impaired ANP Secretion of Atria from Spontaneously Hypertensive Rats

2021 ◽  
Author(s):  
Hye Yoom Kim ◽  
You Mee Ahn ◽  
Se Won Na ◽  
Youn Jae Jang ◽  
Dae Gill Kang ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Renin Angiotensin System ◽  
Positive Control ◽  
Receptor Expression ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Mas Receptor ◽  
Channel Expression

Abstract Background: Oryeongsan (ORS), a herbal medicine formula, has long been used for the treatment of impaired body water balance in Asian countries. Recently, it was shown that ORS modulates the renin-angiotensin system (RAS). Purpose of the present study was to determine characteristics of atrial ANP secretion and effects of ORS on the secretion in the atria from spontaneously hypertensive rats (SHR). Methods: WKY-V treated with vehicle, SHR groups treated with vehicle (SHR-V), ORS (SHR-ORS), and losartan as a positive control (SHR-LOS). Experiments were performed in perfused beating atria (1.3 Hz) allowing atrial distension, acetylcholine (ACh) stimulation, and serial collection of atrial perfusates. The secreted ANP concentration was measured using radioimmunoassay. Interstitial fluid (ISF) translocation was measured using [3H]inulin clearance. Results: Stepwise increase in atrial distension by 1.1, 2.0, and 2.7 cmH2O above basal distension further increased ANP secretion proportionally in the atria from WKY-V, but the response was significantly suppressed in the atria from SHR-V. Cardiomyocyte ANP release, the first step of atrial ANP secretion, was suppressed in the atria from SHR-V compared to those from WKY-V (-8.02 ± 2.86, -15.86 ± 2.27, and -20.09 ± 3.62%; n = 8, vs. 8.59 ± 2.81, 15.65 ± 7.14, and 38.12 ± 8.28%; n = 8; p < 0.001 for all stepwise distension, respectively). Subacute treatment with ORS reversed the suppressed ANP release in atria from SHR-ORS (6.76 ± 3.92, 9.12 ± 2.85, and 28.79 ± 1.79% for SHR-ORS; n = 5 vs. SHR-V; n = 8; p = 0.01, p < 0.001, p < 0.001, respectively). The effects of ORS were comparable to those of losartan. ISF translocation was not significantly different between groups except SHR-V. ACh-induced ANP secretion and cardiomyocyte ANP release were also suppressed in the atria from SHR-V and ORS reversed the suppression. These findings were accompanied with accentuation of the AT1 receptor expression and suppression of the AT2/Mas receptor, M2 mACh receptor and GIRK4 expression in the atria from SHR-V. Further, treatment with ORS or losartan reversed the expressions. Conclusions: These results show that ANP secretion is suppressed in the atria from SHR in association with accentuation of AT1 receptor and suppression of AT2/Mas receptor and KACh channel expression. ORS ameliorates impaired ANP secretion through improving cardiomyocyte ANP release with modulation of the cardiac RAS and muscarinic signaling. These findings provide experimental evidence which supports the role of ORS in the regulation of atrial ANP secretion in the atria from SHR.

Role of genetic variability in the renin-angiotensin system in diabetic and nondiabetic renal disease

2001 ◽  
Vol 21 (6) ◽  
pp. 580-592 ◽  
Author(s):  
Arnold Boonstra ◽  
Dick de Zeeuw ◽  
Paul E. de Jong ◽  
Gerjan Navis
Keyword(s):  
Genetic Variability ◽  
Renal Disease ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

The Renin Angiotensin System and Bipolar Disorder: A Systematic Review

2020 ◽  
Vol 27 (6) ◽  
pp. 520-528 ◽  
Author(s):  
Izabela Guimarães Barbosa ◽  
Giulia Campos Ferreira ◽  
Diomildo Ferreira Andrade Júnior ◽  
Cássio Rocha Januário ◽  
André Rolim Belisário ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bipolar Disorder ◽  
Cardiovascular Diseases ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Angiotensin Receptors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Search Terms

Bipolar Disorder (BD) is a chronic a multifactorial psychiatric illness that affects mood, cognition, and functioning. BD is associated with several psychiatric conditions as well clinical comorbidities, particularly cardiovascular diseases. The neurobiology of BD is complex and multifactorial and several systems have been implicated. Considering that the Renin Angiotensin System (RAS) plays an important role in cardiovascular diseases and that recently evidence has suggested its role in psychiatric disorders, the aim of the present study is to summarize and to discuss recent findings related to the modulation of RAS components in BD. A systematic search of the literature using the electronic databases MEDLINE and LILACS was conducted through March 2019. The search terms were: “Bipolar Disorder”; “Renin Angiotensin System”; “Angiotensin 2”; “Angiotensin receptors”; “Angiotensin 1-7”; “ACE”; “ACE2”; “Mas Receptor”. We included original studies assessing RAS in BD patients. Two hundred twenty-two citations were initially retrieved. Eleven studies were included in our systematic review. In the majority of studies (6 of 8), the ACE insertion/deletion (I/D) polymorphism did not differ between BD patients and controls. BD patients presented higher plasma renin activity in comparison with controls. The studies evaluating the RAS molecules in BD are very scarce and heterogeneous. The literature suggests a potential role of RAS in BD. Further studies are necessary to investigate this relationship.

scholarly journals The Role of the CpG Island Methylator Phenotype in Colorectal Cancer Prognosis Depends on Microsatellite Instability Screening Status

2010 ◽  
Vol 16 (6) ◽  
pp. 1845-1855 ◽  
Author(s):  
Anna M. Dahlin ◽  
Richard Palmqvist ◽  
Maria L. Henriksson ◽  
Maria Jacobsson ◽  
Vincy Eklöf ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cpg Island ◽  
Cancer Prognosis ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype

scholarly journals Hyperactivated RAGE in Comorbidities as a Risk Factor for Severe COVID-19—The Role of RAGE-RAS Crosstalk

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 876
Author(s):  
Sara Chiappalupi ◽  
Laura Salvadori ◽  
Rosario Donato ◽  
Francesca Riuzzi ◽  
Guglielmo Sorci
Keyword(s):  
Gene Polymorphisms ◽  
Renin Angiotensin System ◽  
Molecular Target ◽  
Advanced Glycation ◽  
Angiotensin System ◽  
Major Player ◽  
Glycation End Products ◽  
End Products ◽  
And Oxidative Stress

The receptor for advanced glycation-end products (RAGE) is a multiligand receptor with a role in inflammatory and pulmonary pathologies. Hyperactivation of RAGE by its ligands has been reported to sustain inflammation and oxidative stress in common comorbidities of severe COVID-19. RAGE is essential to the deleterious effects of the renin–angiotensin system (RAS), which participates in infection and multiorgan injury in COVID-19 patients. Thus, RAGE might be a major player in severe COVID-19, and appears to be a useful therapeutic molecular target in infections by SARS-CoV-2. The role of RAGE gene polymorphisms in predisposing patients to severe COVID-19 is discussed. 

scholarly journals Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 205
Author(s):  
Carmen Griñan-Lison ◽  
Jose L. Blaya-Cánovas ◽  
Araceli López-Tejada ◽  
Marta Ávalos-Moreno ◽  
Alba Navarro-Ocón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Progression ◽  
Redox Homeostasis ◽  
Breast Carcinogenesis ◽  
Breast Cancer Patients ◽  
Chemopreventive Agents ◽  
Low Degree ◽  
Potential Use

Breast cancer is the most frequent cancer and the leading cause of cancer death in women. Oxidative stress and the generation of reactive oxygen species (ROS) have been related to cancer progression. Compared to their normal counterparts, tumor cells show higher ROS levels and tight regulation of REDOX homeostasis to maintain a low degree of oxidative stress. Traditionally antioxidants have been extensively investigated to counteract breast carcinogenesis and tumor progression as chemopreventive agents; however, there is growing evidence indicating their potential as adjuvants for the treatment of breast cancer. Aimed to elucidate whether antioxidants could be a reality in the management of breast cancer patients, this review focuses on the latest investigations regarding the ambivalent role of antioxidants in the development of breast cancer, with special attention to the results derived from clinical trials, as well as their potential use as plausible agents in combination therapy and their power to ameliorate the side effects attributed to standard therapeutics. Data retrieved herein suggest that antioxidants play an important role in breast cancer prevention and the improvement of therapeutic efficacy; nevertheless, appropriate patient stratification based on “redoxidomics” or tumor subtype is mandatory in order to define the dosage for future standardized and personalized treatments of patients.

scholarly journals TCA Cycle and Fatty Acids Oxidation Reflect Early Cardiorenal Damage in Normoalbuminuric Subjects with Controlled Hypertension

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1100
Author(s):  
Aranzazu Santiago-Hernandez ◽  
Marta Martin-Lorenzo ◽  
Ariadna Martin-Blazquez ◽  
Gema Ruiz-Hurtado ◽  
Maria G Barderas ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Tricarboxylic Acid Cycle ◽  
Renin Angiotensin System ◽  
Roc Curves ◽  
Tca Cycle ◽  
Urinary Metabolites ◽  
Organ Damage ◽  
Fatty Acid Binding ◽  
Angiotensin System

Moderately increased albuminuria, defined by an albumin to creatinine ratio (ACR) > 30 mg/g, is an indicator of subclinical organ damage associated with a higher risk of cardiovascular and renal disease. Normoalbuminuric subjects are considered at no cardiorenal risk in clinical practice, and molecular changes underlying early development are unclear. To decipher subjacent mechanisms, we stratified the normoalbuminuria condition. A total of 37 hypertensive patients under chronic renin–angiotensin system (RAS) suppression with ACR values in the normoalbuminuria range were included and classified as control (C) (ACR < 10 mg/g) and high-normal (HN) (ACR = 10–30 mg/g). Target metabolomic analysis was carried out by liquid chromatography and mass spectrometry to investigate the role of the cardiorenal risk urinary metabolites previously identified. Besides this, urinary free fatty acids (FFAs), fatty acid binding protein 1 (FABP1) and nephrin were analyzed by colorimetric and ELISA assays. A Mann–Whitney test was applied, ROC curves were calculated and Spearman correlation analysis was carried out. Nine metabolites showed significantly altered abundance in HN versus C, and urinary FFAs and FABP1 increased in HN group, pointing to dysregulation in the tricarboxylic acid cycle (TCA) cycle and fatty acids β-oxidation. We showed here how cardiorenal metabolites associate with albuminuria, already in the normoalbuminuric range, evidencing early renal damage at a tubular level and suggesting increased β-oxidation to potentially counteract fatty acids overload in the HN range.

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