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

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.

Keywords

Heart failure / cardiorenal syndrome / extracellular vesicles / kidney-on-Chip / miRNA

References

[1] Jang KJ,Hamilton GA.Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment.Integr Biol (Camb)2013;5:1119-29

[2] Chatterjee E,Kujala V.Circulating extracellular vesicles in human cardiorenal syndrome promote renal injury in a kidney-on-chip system.JCI Insight2023;8:e165172. PMCID:PMC10721327

[3] Bongartz LG,Doevendans PA,Braam B.The severe cardiorenal syndrome: ‘Guyton revisited’.Eur Heart J2005;26:11-7

[4] Ronco C,House AA,Bellomo R.Cardiorenal syndrome.J Am Coll Cardiol2008;52:1527-39

[5] Bock JS.Cardiorenal syndrome: new perspectives.Circulation2010;121:2592-600

[6] Becker GJ.Animal models of chronic kidney disease: useful but not perfect.Nephrol Dial Transplant2013;28:2432-8

[7] Sepúlveda F,Guzmán K,Lobos-González L.EV-miRNA-mediated intercellular communication in the breast tumor microenvironment.Int J Mol Sci2023;24:13085 PMCID:PMC10487525

[8] Valkov N,Tucker NR.SnRNA sequencing defines signaling by RBC-derived extracellular vesicles in the murine heart.Life Sci Alliance2021;4:e202101048 PMCID:PMC8548207

[9] Alberro A,Fernandes A.Extracellular vesicles in blood: sources, effects, and applications.Int J Mol Sci2021;22:8163 PMCID:PMC8347110

[10] Li Y,Li Q.EV-origin: enumerating the tissue-cellular origin of circulating extracellular vesicles using exLR profile.Comput Struct Biotechnol J2020;18:2851-9 PMCID:PMC7588739

[11] Carris NW,Coughlin E,Tipparaju SM.Novel biomarkers of inflammation in heart failure with preserved ejection fraction: analysis from a large prospective cohort study.BMC Cardiovasc Disord2022;22:221 PMCID:PMC9107006

[12] Walravens AS,Li L.Mechanistic and therapeutic distinctions between cardiosphere-derived cell and mesenchymal stem cell extracellular vesicle non-coding RNA.Sci Rep2021;11:8666 PMCID:PMC8060398