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

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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Protective Role of the ACE2/Ang-(1–9) Axis in Cardiovascular Remodeling

International Journal of Hypertension ◽

10.1155/2012/594361 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 22

Author(s):

María Paz Ocaranza ◽

Jorge E. Jalil

Keyword(s):

Heart Failure ◽

Renin Angiotensin System ◽

Organ Damage ◽

Protective Role ◽

Angiotensin System ◽

Cardiovascular Remodeling ◽

End Organ Damage ◽

Cv Disease

Despite reduction in cardiovascular (CV) events and end-organ damage with the current pharmacologic strategies, CV disease remains the primary cause of death in the world. Pharmacological therapies based on the renin angiotensin system (RAS) blockade are used extensively for the treatment of hypertension, heart failure, and CV remodeling but in spite of their success the prevalence of end-organ damage and residual risk remain still high. Novel approaches must be discovered for a more effective treatment of residual CV remodeling and risk. The ACE2/Ang-(1–9) axis is a new and important target to counterbalance the vasoconstrictive/proliferative RAS axis. Ang-(1–9) is hydrolyzed slower than Ang-(1–7) and is able to bind the Ang II type 2 receptor. We review here the current experimental evidence suggesting that activation of the ACE2/Ang-(1–9) axis protects the heart and vessels (and possibly the kidney) from adverse cardiovascular remodeling in hypertension as well as in heart failure.

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

Seminars in Nephrology ◽

10.1053/snep.2001.26804 ◽

2001 ◽

Vol 21 (6) ◽

pp. 580-592 ◽

Cited By ~ 8

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

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The Renin Angiotensin System and Bipolar Disorder: A Systematic Review

Protein and Peptide Letters ◽

10.2174/0929866527666200127115059 ◽

2020 ◽

Vol 27 (6) ◽

pp. 520-528 ◽

Cited By ~ 2

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.

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Effect of Huangqin Tang on Urine Metabolic Profile in Rats with Ulcerative Colitis Based on UPLC-Q-Exactive Orbitrap MS

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/1874065 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Dunfang Wang ◽

Xuran Ma ◽

Shanshan Guo ◽

Yanli Wang ◽

Tao Li ◽

...

Keyword(s):

Ulcerative Colitis ◽

Fatty Acids ◽

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Unsaturated Fatty Acids ◽

Tricarboxylic Acid Cycle ◽

Tca Cycle ◽

Q Exactive ◽

Therapeutic Mechanisms

As a classic prescription, Huangqin Tang (HQT) has been widely applied to treat ulcerative colitis (UC), although its pharmacological mechanisms are not clear. In this study, urine metabolomics was first analysed to explore the therapeutic mechanisms of HQT in UC rats induced by TNBS. We identified 28 potential biomarkers affected by HQT that might cause changes in urine metabolism in UC rats, mapped the network of metabolic pathways, and revealed how HQT affects metabolism of UC rats. The results showed that UC affects amino acid metabolism and biosynthesis of unsaturated fatty acids and impairs the tricarboxylic acid cycle (TCA cycle). UC induced inflammatory and gastrointestinal reactions by inhibiting the transport of fatty acids and disrupting amino acid metabolism. HQT plays key roles via regulating the level of biomarkers in the metabolism of amino acids, lipids, and so on, normalizing metabolic disorders. In addition, histopathology and other bioinformatics analysis further confirm that HQT altered UC rat physiology and pathology, ultimately affecting metabolic function of UC rats.

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

Biomolecules ◽

10.3390/biom11060876 ◽

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.

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