Characterization of pendrin in urinary extracellular vesicles in a rat model of aldosterone excess and in human primary aldosteronism
| Autor: | Kenichi Ishizawa, Osamu Yamazaki, Daigoro Hirohama, Yoshihide Fujigaki, Michito Nagura, Fumika Ochiai-Homma, Shinichiro Asakawa, Wataru Fujii, Shigeru Shibata, Masataka Murakawa, Tetsuo Nishikawa, Kohei Odajima, Shigeyuki Arai, Mika Kawagoe, Yoshihiro Tomomitsu, Yuya Tsurutani, Yoshifuru Tamura, Emiko Kuribayashi-Okuma |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Epithelial sodium channel medicine.medical_specialty Physiology medicine.drug_class Urinary system Urine 030204 cardiovascular system & hematology Transporter Exosomes Article Extracellular Vesicles 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Primary aldosteronism Mineralocorticoid receptor Mineralocorticoids Internal medicine Hyperaldosteronism otorhinolaryngologic diseases Internal Medicine medicine Animals Humans Chloride-Bicarbonate Antiporters Aldosterone Kidney biology Pendrin medicine.disease Rats Exosome Cross-Sectional Studies 030104 developmental biology Endocrinology medicine.anatomical_structure Mineralocorticoid chemistry Sulfate Transporters Hypertension biology.protein Cardiology and Cardiovascular Medicine Biomarkers |
| Zdroj: | Hypertension Research |
| ISSN: | 1348-4214 0916-9636 |
| DOI: | 10.1038/s41440-021-00710-5 |
| Popis: | Pendrin is a Cl−/HCO3− exchanger selectively present in the intercalated cells of the kidney. Although experimental studies have demonstrated that pendrin regulates blood pressure downstream of the renin-angiotensin-aldosterone system, its role in human hypertension remains unclear. Here, we analyzed the quantitative changes in pendrin in urinary extracellular vesicles (uEVs) isolated from a total of 30 patients with primary aldosteronism (PA) and from a rat model of aldosterone excess. Western blot analysis revealed that pendrin is present in dimeric and monomeric forms in uEVs in humans and rats. In a rodent model that received continuous infusion of aldosterone with or without concomitant administration of the selective mineralocorticoid receptor (MR) antagonist esaxerenone, pendrin levels in uEVs, as well as those of epithelial Na+ channel (ENaC) and Na-Cl-cotransporter (NCC), were highly correlated with renal abundance. In patients with PA, pendrin levels in uEVs were reduced by 49% from baseline by adrenalectomy or pharmacological MR blockade. Correlation analysis revealed that the magnitude of pendrin reduction after treatment significantly correlated with the baseline aldosterone-renin ratio (ARR). Finally, a cross-sectional analysis of patients with PA confirmed a significant correlation between the ARR and pendrin levels in uEVs. These data are consistent with experimental studies showing the role of pendrin in aldosterone excess and suggest that pendrin abundance is attenuated by therapeutic interventions in human PA. Our study also indicates that pendrin analysis in uEVs, along with other proteins, can be useful to understand the pathophysiology of hypertensive disorders. |
| Databáze: | OpenAIRE |
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