Renal Sodium Transporters Are Increased in Urinary Exosomes of Cyclosporine-Treated Kidney Transplant Patients

Esteva‐Font, Cristina; Guillén‐Gómez, Elena; Díaz, Joan Manuel; Guirado, Luís; Facundo, Carmen; Ars, Elisabet; Ballarín, J.; Fernández-Llama, Patricia

doi:10.1159/000362905

Cited by 31 publications

(19 citation statements)

References 33 publications

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“…Recent studies have confirmed that urinary exosomal content is altered by RAAS activation [71]. The levels of exosomal sodium transporters including sodium chloride cotransporter, alpha- and gamma-epithelial sodium channels were strongly correlated with the progression of hypertension [71–75]. The miRNome analysis of urinary exosomes from hypertensive patients also proved that several miRNAs like miR-615, miR-211 were sensitive to fluctuation of blood pressure [76].…”

Section: Role Of Exosomes In Vascular Diseasementioning

confidence: 99%

Emerging role of exosome-mediated intercellular communication in vascular remodeling

Xie

et al. 2017

Oncotarget

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Vascular remodeling refers to the alternations of function and structure in vasculature. A complex autocrine/paracrine set of cellular interaction is involved in vascular remodeling. Exosome, a newly identified natural nanocarrier and intercellular messenger, plays a pivotal role in regulating cell-to-cell communication. Exosome emerges as an important mediator in the process of vascular remodeling, showing the most prognostic and therapeutic potent in vascular diseases. Benefiting from exosomal trafficking, the vasculature can not only maintain its function and structure in physiological condition, but also adapt itself in pathological status. In this review, we will represent the roles of exosomes in angiogenesis, endothelial function and cardiac regeneration. In addition, greatly depending on the pathophysiological status of donor cells and peripheral micro-circumstance, the exosomal content could alter, which makes exosomes exhibit pleiotropic effects in vascular diseases. Hence, the diverse effects of exosomes in vascular diseases including atherosclerosis, neointima formation and vascular repair, primary hypertension, pulmonary artery hypertension, and aortic aneurysm will be discussed. Finally, the translational appliances targeting exosomes will be concluded by providing updated applications of engineered exosomes in clinic.

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Section: Role Of Exosomes In Vascular Diseasementioning

confidence: 99%

Emerging role of exosome-mediated intercellular communication in vascular remodeling

Xie

et al. 2017

Oncotarget

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“…Anyway, in transplanted patients, uEVs may represent a potential source for markers of drug toxicity. For example, a significant increase of NKCC2 and Na-Cl co-transporter was found in uEVs from cyclosporine-treated kidney transplanted patients compared with the controls (Esteva-Font et al, 2014). …”

Section: Evs As Renal Disease Biomarkersmentioning

confidence: 99%

Extracellular Vesicles in Renal Pathophysiology

Pomatto

Gai

Bussolati

et al. 2017

Front. Mol. Biosci.

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Extracellular vesicles are a heterogeneous population of microparticles released by virtually all living cells which have been recently widely investigated in different biological fields. They are typically composed of two primary types (exosomes and microvesicles) and are recently commanding increasing attention as mediators of cellular signaling. Indeed, these vesicles can affect recipient cells by carrying and delivering complex cargos of biomolecules (including proteins, lipids and nucleic acids), protected from enzymatic degradation in the environment. Their importance has been demonstrated in the pathophysiology of several organs, in particular in kidney, where different cell types secrete extracellular vesicles that mediate their communication with downstream urinary tract cells. Over the past few years, evidence has been shown that vesicles participate in kidney development and normal physiology. Moreover, EVs are widely demonstrated to be implicated in cellular signaling during renal regenerative and pathological processes. Although many EV mechanisms are still poorly understood, in particular in kidney, the discovery of their role could help to shed light on renal biological processes which are so far elusive. Lastly, extracellular vesicles secreted by renal cells gather in urine, thus becoming a great resource for disease or recovery markers and a promising non-invasive diagnostic instrument for renal disease. In the present review, we discuss the most recent findings on the role of extracellular vesicles in renal physiopathology and their potential implication in diagnosis and therapy.

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“…Esteva-Font et al . found a positive correlation between plasma CsA levels and NCC abundance in uEVs of CsA-treated kidney transplant recipients [37]. Rojas-Vega et al .…”

Section: Introductionmentioning

confidence: 99%

NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity

et al. 2017

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Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles (uEVs) after internalization into multivesicular bodies. Human studies indicate that CNIs also increase NCC abundance in uEVs, but results are conflicting and no relationship with NCC function has been shown. Therefore, we investigated the effects of CsA and Tac on the abundance of both total NCC (tNCC) and phosphorylated NCC at Thr60 phosphorylation site (pNCC) in uEVs, and assessed whether NCC abundance in uEVs predicts the blood pressure response to thiazide diuretics. Our results show that in kidney transplant recipients treated with cyclosporine (n = 9) or tacrolimus (n = 23), the abundance of both tNCC and pNCC in uEVs is 4–5 fold higher than in CNI-free kidney transplant recipients (n = 13) or healthy volunteers (n = 6). In hypertensive kidney transplant recipients, higher abundances of tNCC and pNCC prior to treatment with thiazides predicted the blood pressure response to thiazides. During thiazide treatment, the abundance of pNCC in uEVs increased in responders (n = 10), but markedly decreased in non-responders (n = 8). Thus, our results show that CNIs increase the abundance of both tNCC and pNCC in uEVs, and these increases correlate with the blood pressure response to thiazides. This implies that assessment of NCC in uEVs could represent an alternate method to guide anti-hypertensive therapy in kidney transplant recipients.

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Renal Sodium Transporters Are Increased in Urinary Exosomes of Cyclosporine-Treated Kidney Transplant Patients

Cited by 31 publications

References 33 publications

Emerging role of exosome-mediated intercellular communication in vascular remodeling

Emerging role of exosome-mediated intercellular communication in vascular remodeling

Extracellular Vesicles in Renal Pathophysiology

NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity

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