Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria

Martin‐Lorenzo, Marta; González-Calero, Laura; Martínez, Pedro Luis Moreno; Baldán-Martín, Montserrat; López, Juan Antonio; Ruiz‐Hurtado, Gema; Cuesta, Fernando de la; Segura, Julián; Vázquez, Jesús; Vivanco, Fernando; Barderas, María G.; Ruilope, Luís M.; Alvarez-Llamas, Gloria

doi:10.1038/s41598-017-09042-2

Cited by 15 publications

(9 citation statements)

References 55 publications

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“…The signatures were composed of proteins involved in inflammation, immune, and proteasome activation/endoplasmatic reticulum stress. Further studies by these authors in urine samples [78] and urinary exosomes [79] confirmed the link between inflammation and development of albuminuria in people with controlled hypertension on RAAS blockade. The complementary nature of these two studies using different sample types increases the reliability of the data and paves the way to further studies that can explore effects of therapeutic strategies on proteomic signatures of immune dysregulation that will translate into prevention of albuminuria and ultimately, renal failure in patients with hypertension.…”

Section: Human Studiesmentioning

confidence: 86%

Utilizing proteomics to understand and define hypertension: where are we and where do we go?

Delles

Carrick

Graham

et al. 2018

Expert Review of Proteomics

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Introduction: Hypertension is a complex and multifactorial cardiovascular disorder. With different mechanisms contributing to a different extent to an individual’s blood pressure, the discovery of novel pathogenetic principles of hypertension is challenging. However, there is an urgent and unmet clinical need to improve prevention, detection, and therapy of hypertension in order to reduce the global burden associated with hypertension-related cardiovascular diseases.Areas covered: Proteomic techniques have been applied in reductionist experimental models including angiotensin II infusion models in rodents and the spontaneously hypertensive rat in order to unravel mechanisms involved in blood pressure control and end organ damage. In humans proteomic studies mainly focus on prediction and detection of organ damage, particularly of heart failure and renal disease. While there are only few proteomic studies specifically addressing human primary hypertension, there are more data available in hypertensive disorders in pregnancy, such as preeclampsia. We will review these studies and discuss implications of proteomics on precision medicine approaches.Expert commentary: Despite the potential of proteomic studies in hypertension there has been moderate progress in this area of research. Standardized large-scale studies are required in order to make best use of the potential that proteomics offers in hypertension and other cardiovascular diseases.

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Section: Human Studiesmentioning

confidence: 86%

Utilizing proteomics to understand and define hypertension: where are we and where do we go?

Delles

Carrick

Graham

et al. 2018

Expert Review of Proteomics

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“…Targeted mass spectrometry analysis was accomplished by Selected Reaction Monitoring (SRM-LC-MS/MS) methodology as previously published [ 12 , 15 ]. A 6460 Triple Quadrupole QQQ on-line connected to HPLC (1200 Series) controlled by Mass Hunter Acquisition Software (v4.01) (Agilent Technologies) was used.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting

et al. 2021

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Atherosclerosis is the predominant pathology associated to premature deaths due to cardiovascular disease. However, early intervention based on a personalized diagnosis of cardiovascular risk is very limited. We have previously identified metabolic alterations during atherosclerosis development in a rabbit model and in subjects suffering from an acute coronary syndrome. Here we aim to identify specific metabolic signatures which may set the basis for novel tools aiding cardiovascular risk diagnosis in clinical practice. In a cohort of subjects with programmed coronary artery bypass grafting (CABG), we have performed liquid chromatography and targeted mass spectrometry analysis in urine and plasma. The role of vascular smooth muscle cells from human aorta (HA-VSMCs) was also investigated by analyzing the intra and extracellular metabolites in response to a pro-atherosclerotic stimulus. Statistically significant variation was considered if p value < 0.05 (Mann-Whitney test). Urinary trimethylamine N-oxide (TMAO), arabitol and spermidine showed higher levels in the CVrisk group compared with a control group; while glutamine and pantothenate showed lower levels. The same trend was found for plasma TMAO and glutamine. Plasma choline, acetylcholine and valine were also decreased in CVrisk group, while pyruvate was found increased. In the secretome of HA-VSMCs, TMAO, pantothenate, glycerophosphocholine, glutathion, spermidine and acetylcholine increased after pro-atherosclerotic stimulus, while secreted glutamine decreased. At intracellular level, TMAO, pantothenate and glycerophosphocholine increased with stimulation. Observed metabolic deregulations pointed to an inflammatory response together with a deregulation of oxidative stress counteraction.

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“…Based on urinary proteomic analysis, researchers have identified C3 as a pathogenic marker associated with albuminuria development in hypertensive patients with chronic renin-angiotensin system (RAS) suppression. 25 The hypertensive rat model also emphasizes the crucial role of the complement system in renal function reduction. 26 Recently, the activation of the complement AP has been a hot spot on the pathogenesis of malignant hypertension.…”

Section: Activation Of the Complement Ap In Subjects With Hypertensiv...mentioning

confidence: 99%

The potential role of complement alternative pathway activation in hypertensive renal damage

Wang

Zhang

2022

Exp Biol Med (Maywood)

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Hypertensive renal damage is a common secondary kidney disease caused by poor control of blood pressure. Recent evidence has revealed abnormal activation of the complement alternative pathway (AP) in hypertensive patients and animal models and that this phenomenon is related to hypertensive renal damage. Conditions in the setting of hypertension, including high renin concentration, reduced binding of factor H to the glomerular basement membrane, and abnormal local synthesis of complement proteins, potentially promote the AP activation in the kidney. The products of the AP activation promote the phenotypic transition of mesangial cells and tubular cells, attack endothelial cells and recruit immunocytes to worsen hypertensive renal damage. The effects of complement inhibition on hypertensive renal damage are contradictory. Although clinical data support the use of C5 monoclonal antibody in malignant hypertension, pharmacological inhibition in hypertensive animals provides little benefit to kidney function. Therefore, the role of the complement AP in the pathogenesis of hypertensive renal damage and the value of complement inhibition in hypertensive renal damage treatment must be further explored.

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Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria

Cited by 15 publications

References 55 publications

Utilizing proteomics to understand and define hypertension: where are we and where do we go?

Utilizing proteomics to understand and define hypertension: where are we and where do we go?

Metabolic Alterations Identified in Urine, Plasma and Aortic Smooth Muscle Cells Reflect Cardiovascular Risk in Patients with Programmed Coronary Artery Bypass Grafting

The potential role of complement alternative pathway activation in hypertensive renal damage

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