scholarly journals Loss of Hepatic Angiotensinogen Attenuates Sepsis-Induced Myocardial Dysfunction

2021 ◽  
Author(s):  
Jiabing Rong ◽  
Xinran Tao ◽  
Yao Lin ◽  
Haiqiong Zheng ◽  
Le Ning ◽  
...  
Keyword(s):  
Cardiac Fibroblasts ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Ldl Receptor ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Angiotensin Peptides ◽  
Plasmic Reticulum ◽  
Underlying Mechanisms

Rationale: The renin-angiotensin system (RAS) is a complex regulatory network that maintains normal physiological functions. The role of the RAS in sepsis-induced myocardial dysfunction (SIMD) is poorly defined. Angiotensinogen (AGT) is the unique precursor of the RAS and gives rise to all angiotensin peptides. The effects and mechanisms of AGT in development of SIMD have not been defined. Objective: To determine a role of AGT in SIMD and investigate the underlying mechanisms. Methods and Results: Either intraperitoneal injection of lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) significantly enhanced AGT abundances in liver, heart, and plasma. Deficiency of hepatocyte-derived AGT (hepAGT), rather than cardiomyocyte-derived AGT (carAGT), alleviated septic cardiac dysfunction in mice and prolonged survival time. Further investigations revealed that the effects of hepAGT on SIMD were partially associated with augmented angiotensin II (AngII) production in circulation. In addition, hepAGT was internalized by LDL receptor-related protein 1 (LRP1) in cardiac fibroblasts (CF), and subsequently activated NLRP3 inflammasome via an AngII-independent pathway, ultimately promoting SIMD by suppressing Sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) abundances in cardiomyocytes (CM). Conclusions: HepAGT promoted SIMD via both AngII-dependent and AngII-independent pathways. We identified a liver-heart axis by which AGT regulated development of SIMD. Our study may provide a potential novel therapeutic target for SIMD.

scholarly journals ACE2/ANG-(1–7)/Mas pathway in the brain: the axis of good

2011 ◽  
Vol 300 (4) ◽  
pp. R804-R817 ◽  
Author(s):  
Ping Xu ◽  
Srinivas Sriramula ◽  
Eric Lazartigues
Keyword(s):  
Neurological Diseases ◽  
Renin Angiotensin System ◽  
Transgenic Animals ◽  
Angiotensin Iv ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Mas Receptor ◽  
Angiotensin Peptides ◽  
The Central Nervous System

The last decade has seen the discovery of several new components of the renin-angiotensin system (RAS). Among them, angiotensin converting enzyme-2 (ACE2) and the Mas receptor have forced a reevaluation of the original cascade and led to the emergence of a new arm of the RAS: the ACE2/ANG-(1–7)/Mas axis. Accordingly, the new system is now seen as a balance between a provasoconstrictor, profibrotic, progrowth axis (ACE/ANG-II/AT1 receptor) and a provasodilatory, antifibrotic, antigrowth arm (ACE2/ANG-(1–7)/Mas receptor). Already, this simplistic vision is evolving and new components are branching out upstream [ANG-(1–12) and (pro)renin receptor] and downstream (angiotensin-IV and other angiotensin peptides) of the classical cascade. In this review, we will summarize the role of the ACE2/ANG-(1–7)/Mas receptor, focusing on the central nervous system with respect to cardiovascular diseases such as hypertension, chronic heart failure, and stroke, as well as neurological diseases. In addition, we will discuss the new pharmacological (antagonists, agonists, activators) and genomic (knockout and transgenic animals) tools that are currently available. Finally, we will review the latest data regarding the various signaling pathways downstream of the Mas receptor.

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.

scholarly journals Effects of Statins on Renin–Angiotensin System

2021 ◽  
Vol 8 (7) ◽  
pp. 80
Author(s):  
Nasim Kiaie ◽  
Armita Mahdavi Gorabi ◽  
Željko Reiner ◽  
Tannaz Jamialahmadi ◽  
Massimiliano Ruscica ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Ras Pathway ◽  
Renin Angiotensin ◽  
Wide Range ◽  
Integral Role ◽  
Underlying Mechanisms ◽  
Therapeutic Possibilities

Statins, a class of drugs for lowering serum LDL-cholesterol, have attracted attention because of their wide range of pleiotropic effects. An important but often neglected effect of statins is their role in the renin–angiotensin system (RAS) pathway. This pathway plays an integral role in the progression of several diseases including hypertension, heart failure, and renal disease. In this paper, the role of statins in the blockade of different components of this pathway and the underlying mechanisms are reviewed and new therapeutic possibilities of statins are suggested.

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 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 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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