Dataset Information

Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria.

ABSTRACT: Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria development: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Quantitative analysis was performed in a first discovery cohort by isobaric labeling methodology. Alterations of proteins of interest were confirmed by target mass spectrometry analysis in an independent cohort. A total of 2416 proteins and 1223 functional categories (coordinated protein responses) were identified. Immune response, adhesion of immune and blood cells, and phagocytosis were found significantly altered in patients with albuminuria compared to normoalbuminuric individuals. The complement system C3 increases, while Annexin A1, CD44, S100A8 and S100A9 proteins showed significant diminishment in their urinary levels when albuminuria is present. This study reveals specific links between immune response and controlled hypertension in patients who develop albuminuria, pointing to potential protein targets for novel and future therapeutic interventions.

SUBMITTER: Martin-Lorenzo M

PROVIDER: S-EPMC5566220 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria.

Martin-Lorenzo Marta M Gonzalez-Calero Laura L Martinez Paula J PJ Baldan-Martin Montserrat M Lopez Juan Antonio JA Ruiz-Hurtado Gema G de la Cuesta Fernando F Segura Julián J Vazquez Jesús J Vivanco Fernando F Barderas Maria G MG Ruilope Luis M LM Alvarez-Llamas Gloria G

Scientific reports 20170821 1

Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria development: ...[more]

PMID: 28827575

Similar Datasets

Project description:BACKGROUND:Hypertension is a multi-factorial disease of increasing prevalence and a major risk factor for cardiovascular mortality even in the presence of adequate treatment. Progression of cardiovascular disease (CVD) occurs frequently during chronic renin-angiotensin-system (RAS) suppression, and albuminuria is a marker of CV risk. High prevalence of albuminuria in treated hypertensive patients has been demonstrated, but there are no available markers able to predict evolution. The aim of this study was the identification of novel indicators of albuminuria progression measurable in urine of diabetic and non-diabetic patients. METHODS:1143 hypertensive patients under chronic treatment were followed for a minimum period of 3 years. Among them, 105 diabetic and non-diabetic patients were selected and classified in three groups according to albuminuria development during follow-up: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Differential urine analysis was performed by 2D gel electrophoresis (2D-DIGE) and further confirmed by liquid chromatography-mass spectrometry. Non-parametric statistical tests were applied. RESULTS:CD59 glycoprotein and alpha-1 antitrypsin (AAT) resulted already altered in patients developing albuminuria de novo, with a similar response in those with maintained albuminuria. A prospective study in a sub-group of normoalbuminuric patients who were clinically followed up for at least 1 year from urine sampling, revealed CD59 and AAT proteins significantly varied in the urine collected from normoalbuminurics who will negatively progress, serving as predictors of future albuminuria development. CONCLUSIONS:CD59 and AAT proteins are significantly altered in hypertensive patients developing albuminuria. Interestingly, CD59 and AAT are able to predict, in normoalbuminuric individuals, who will develop albuminuria in the future, being potential predictors of vascular damage and CV risk. These findings contribute to early identify patients at risk of developing albuminuria even when this classical predictor is still in the normal range, constituting a novel strategy towards a prompt and more efficient therapeutic intervention with better outcome.

Project description:PurposeWe investigated the association between albuminuria and hypertensive retinopathy (HR) in hypertensive adults.MethodsThis was a cross-sectional subgroup analysis of data from the China Stroke Primary Prevention Trial. We enrolled 2,964 hypertensive adults in this study. Keith-Wagener-Barker stages was used to assess HR. The urinary albumin to creatinine ratio (UACR) was calculated to evaluate albuminuria.ResultsHR was found in 76.6% (n = 2, 271) of the participants, albuminuria was found in 11.1% (n = 330). The UACR levels were significantly higher in subjects with HR than in those without HR (grade 1, β = 1.42, 95% confidence intervals [CI]: -0.12, 2.95, p = 0.070; grade 2, β = 2.62, 95% CI: 0.56, 4.67, p = 0.013; grade 3, β = 5.17, 95% CI: 1.13, 9.20, p = 0.012). In the subgroup analyses, the association between HR and UACR was stronger in current smokers (p for interaction = 0.014). The correlation between HR grades 1 and 2 and UACR was stronger in subjects with higher triglyceride levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglycerides levels (< 1.7 mmol/L, p for interaction = 0.023). The odds of albuminuria were significantly higher in subjects with HR than in those without HR (grade 1, odds ratio [OR] = 1.57, 95% CI: 1.08, 2.29, p = 0.019; grade 2, OR = 2.02, 95% CI: 1.28, 3.18, p = 0.002; grade 3, OR = 2.12, 95% CI: 0.99, 4.55, p = 0.053). In the subgroup analyses, the association between HR grades 1 and 2 and albuminuria was stronger in subjects with higher triglycerides levels (≥ 1.7 mmol/L), but for grade 3 HR, this correlation was stronger in subjects with lower triglyceride levels (< 1.7 mmol/L, p for interaction = 0.014).ConclusionHR was positively correlated with albuminuria in hypertensive Chinese adults. This correlation was more remarkable when the population was stratified by triglycerides levels and smoking status. HR can be used as an indicator of early renal injury.

Project description:Individuals with diverticula or outpouchings of the colonic mucosa and submucosa through the colonic wall have diverticulosis, which is usually asymptomatic. In 10-25% of individuals, the diverticula become inflamed, resulting in diverticulitis. Very little is known about the pathophysiology or gene regulatory pathways involved in the development of diverticulitis. To identify these pathways, we deep sequenced RNAs isolated from full-thickness sections of sigmoid colon from diverticulitis patients and control individuals. Specifically for diverticulitis cases, we analyzed tissue adjacent to areas affected by chronic disease. Since the tissue was collected during elective sigmoid resection, the disease was in a quiescent state. A comparison of differentially expressed genes found that gene ontology (GO) pathways associated with the immune response were upregulated in diverticulitis patients compared with nondiverticulosis controls. Next, weighted gene coexpression network analysis was performed to identify the interaction among coexpressed genes. This analysis revealed RASAL3, SASH3, PTPRC, and INPP5D as hub genes within the brown module eigengene, which highly correlated (r = 0.67, P = 0.0004) with diverticulitis. Additionally, we identified elevated expression of downstream interacting genes. In summary, transcripts associated with the immune response were upregulated in adjacent tissue from the sigmoid colons of chronic, recurrent diverticulitis patients. Further elucidating the genetic or epigenetic mechanisms associated with these alterations can help identify those at risk for chronic disease and may assist in clinical decision management.NEW & NOTEWORTHY By using an unbiased approach to analyze transcripts expressed in unaffected colonic tissues adjacent to those affected by chronic diverticulitis, our study implicates that a defect in the immune response may be involved in the development of the disease. This finding expands on the current data that suggest the pathophysiology of diverticulitis is mediated by dietary, age, and obesity-related factors. Further characterizing the immunologic differences in diverticulitis may better inform clinical decision-making.

Dataset Information

Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria.

Publications

Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets