Proteomic Profile of Urinary Extracellular Vesicles Identifies AGP1 as a Potential Biomarker of Primary Aldosteronism

Barros, Eric; Rigalli, Juan Pablo; Tapia-Castillo, Alejandra; Vecchiola, Andrea; Young, Morag J.; Hoenderop, Joost G. J.; Bindels, René J. M.; Fardella, Carlos E.; Carvajal, Cristián A.

doi:10.1210/endocr/bqab032

Cited by 13 publications

(19 citation statements)

References 72 publications

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“…We measured the serum levels of lipocalins AGP1, LCN2, and LCN2-MMP9 proteins (26) by commercial ELISA immunoassay for AGP1 (Human a1-Acid Glycoprotein Immunoassay, DAGP00, USA R&D Systems, Inc.) according to the manufacturer's protocol, LCN2 (DLCN20, R&D Systems, Minneapolis, MN), LCN2-MMP9 (DM9L20, R&D Systems, Minneapolis, MN).…”

Section: Determination Of Serum Lipocalins Agp1 Lcn2 and Lcn2-mmp9 In Pa Subjectsmentioning

confidence: 99%

“…Urinary creatinine was used to normalize samples of uEVs (59,60). Isolated uEVs were characterized as previously described (26,31) and according to the International Society for Extracellular Vesicles guidelines (27) using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot with characteristic EV proteins (61).…”

Section: Isolation and Characterization Of Urinary Extracellular Vesicles From Pa Subjectsmentioning

confidence: 99%

“…However, none of these biomarkers are currently available in clinical diagnoses for arterial hypertension or PA. Recent proteomic studies have shown that urinary and serum alpha-1-acid glycoprotein-1 (AGP1), also known as ORM1, have been proposed as prognostic biomarkers for inflammatory diseases such as chronic heart failure (24), some types of cancer (25), and lately for PA (26).…”

Section: Introductionmentioning

confidence: 99%

“…Experimental and clinical studies demonstrate that small extracellular vesicles (sEVs) or exosomes are potential biomarkers of disease (27), including in cancer, metabolic disorders, and cardiovascular diseases (28,29). Urinary EVs originated mainly from cells lining the renal tubules carrying proteins, lipids, RNA, and miRNA, and have been recognized recently as a source of diagnostic biomarkers for different renal and endocrine pathologies (30)(31)(32)(33)(34)(35)(36), including primary aldosteronism (26).…”

Section: Introductionmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are short non-coding RNA molecules genome-encoded, that are approximately 22 nucleotides in length and modulate downstream gene expression by posttranscriptional mechanisms, specifically by binding to the 3′ untranslated regions (UTR) of a target messenger RNA (mRNA), leading to mRNA degradation or repression of translation (37)(38)(39). Recent literature (30,37,(40)(41)(42)(43)(44)(45)(46) proposes that microRNAs in exosomes are involved in physiological and pathophysiological processes correlated with hypertension (47) response to sodium intake (48) and PA (26,30). miRNAs are packaged into EVs for transport into different biofluids (e.g., blood, urine) and change according to the metabolic microenvironment (e.g., inflammation) of the parent cell.…”

Section: Introductionmentioning

confidence: 99%

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Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism

et al. 2021

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Primary aldosteronism (PA) is the most common cause of secondary hypertension and reaches a prevalence of 6-10%. PA is an endocrine disorder, currently identified as a broad-spectrum phenotype, spanning from normotension to hypertension. In this regard, several studies have made advances in the identification of mediators and novel biomarkers of PA as specific proteins, miRNAs, and lately, extracellular vesicles (EVs) and their cargo.AimTo evaluate lipocalins LCN2 and AGP1, and specific urinary EV miR-21-5p and Let-7i-5p as novel biomarkers for PA.Subjects and MethodsA cross-sectional study was performed in 41 adult subjects classified as normotensive controls (CTL), essential hypertensives (EH), and primary aldosteronism (PA) subjects, who were similar in gender, age, and BMI. Systolic (SBP) and diastolic (DBP) blood pressure, aldosterone, plasma renin activity (PRA), and aldosterone to renin ratio (ARR) were determined. Inflammatory parameters were defined as hs-C-reactive protein (hs-CRP), PAI-1, MMP9, IL6, LCN2, LCN2-MMP9, and AGP1. We isolated urinary EVs (uEVs) and measured two miRNA cargo miR-21-5p and Let-7i-5p by Taqman-qPCR. Statistical analyses as group comparisons were performed by Kruskall-Wallis, and discriminatory analyses by ROC curves were performed with SPSS v21 and Graphpad-Prism v9.ResultsPA and EH subjects have significantly higher SBP and DBP (p <0.05) than the control group. PA subjects have similar hs-CRP, PAI-1, IL-6, MMP9, LCN2, and LCN2-MMP9 but have higher levels of AGP1 (p <0.05) than the CTL&EH group. The concentration and size of uEVs and miRNA Let-7i-5p did not show any difference between groups. In PA, we found significantly lower levels of miR-21-5p than controls (p <0.05). AGP1 was associated with aldosterone, PRA, and ARR. ROC curves detected AUC for AGP1 of 0.90 (IC 95 [0.79 – 1.00], p <0.001), and combination of AGP1 and EV-miR-21-5p showed an AUC of 0.94 (IC 95 [0.85 – 1.00], p<0.001) to discriminate the PA condition from EH and controls.ConclusionSerum AGP1 protein was found to be increased, and miR-21-5p in uEVs was decreased in subjects classified as PA. Association of AGP1 with aldosterone, renin activity, and ARR, besides the high discriminatory capacity of AGP1 and uEV-miR-21-5p to identify the PA condition, place both as potential biomarkers of PA.

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Section: Determination Of Serum Lipocalins Agp1 Lcn2 and Lcn2-mmp9 In Pa Subjectsmentioning

confidence: 99%

Section: Isolation and Characterization Of Urinary Extracellular Vesicles From Pa Subjectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism

et al. 2021

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Proteomic characterization of extracellular vesicles in programmed cell death

Xue,

Wong,

Zhao

et al. 2024

Proteomics

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Programmed cell death (PCD) is a fundamental biological process that plays a critical role in cell development, differentiation, and homeostasis. The secretion and uptake of extracellular vesicles (EVs) is one of the important regulatory mechanisms for PCD. EVs are natural membrane structures secreted by cells that contain a variety of proteins, lipids, nucleic acids, and other bioactive molecules. Due to their important roles in intercellular communication and disease progression, there is great interest in studying EVs and their cargo. Different protein components are sorted and packaged in EVs, allowing EVs to perform their functions. The study of EV proteomics helps us understand the role of PCD in the development of diseases. Meanwhile, proteomics is a powerful tool for studying the composition and function of EVs, which assists in the identification, quantification, and profiling of protein components of EVs, and provides insight into the molecular mechanisms involved in PCD and related diseases. In this review, we summarize the characteristics of EV proteomics in different types of PCD, compare different proteomic profiling strategies for EVs, and discuss the impact of EV proteomics on cell function and regulation during PCD, to understand its role in the pathogenesis of related diseases.

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