EV-idence uncovered: kidney-on-chip study links circulating EVs of cardiorenal syndrome to renal pathology.

Extracellular vesicles and circulating nucleic acids Pub Date : 2024-10-26 eCollection Date: 2024-01-01 DOI:10.20517/evcna.2024.70
Hawa Ndiaye, Simran Rajput, John F K Sauld, Gautam Mahajan, Saumya Das, Emeli Chatterjee
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Abstract

The intertwined nature of cardiac and renal failure, where dysfunction in one organ predicts a poor outcome in the other, has long driven the interest in uncovering the exact molecular links between the two. Elucidating the mechanisms driving Cardiorenal Syndrome (CRS) will enable the development of targeted therapies that disrupt this detrimental cycle, potentially improving outcomes for patients. A recent study by Chatterjee et al. (JCI insight 2023) demonstrated the feasibility of utilizing a humanized microfluidic kidney-on-chip model to elucidate the role of circulating extracellular vesicles (EVs) in the development of CRS (type 1 and type 2) in heart failure (HF) patients. The study also identified and validated EV miRNAs that correlated with kidney function by targeting several genes involved in kidney damage pathways, including transforming growth factor- β (TGF-β) signaling. These findings suggest that plasma EVs from CRS patients induce harmful responses in renal cells by regulating key pathways, highlighting their role in both type 1 and type 2 CRS.

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ev证据发现:肾脏芯片研究将心肾综合征循环ev与肾脏病理联系起来。
心脏衰竭和肾功能衰竭相互交织,其中一个器官的功能障碍预示着另一个器官的不良预后。阐明心肾综合征(CRS)的驱动机制将有助于开发能破坏这种有害循环的靶向疗法,从而改善患者的预后。Chatterjee 等人最近的一项研究(JCI insight 2023)证明了利用人源化微流控芯片肾脏模型阐明循环细胞外囊泡(EV)在心力衰竭(HF)患者CRS(1型和2型)发病过程中的作用的可行性。研究还通过靶向参与肾脏损伤通路(包括转化生长因子-β(TGF-β)信号转导)的多个基因,鉴定并验证了与肾功能相关的EV miRNA。这些研究结果表明,CRS 患者的血浆 EVs 通过调节关键通路诱导肾细胞产生有害反应,突出了 EVs 在 1 型和 2 型 CRS 中的作用。
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