Emeli Chatterjee, Rodosthenis S Rodosthenous, Ville J Kujala, Priyanka Gokulnath, Michail Spanos, H Immo Lehmann, Getulio P de Oliveira-Jr, Mingjian Shi, Tyne W Miller-Fleming, Guoping Li, Ionita Ghiran, Katia Karalis, JoAnn Lindenfeld, Jonathan D Mosley, Emily S Lau, Jennifer E Ho, Quanhu Sheng, Ravi Shah, Saumya Das
BACKGROUND: Cardiorenal syndrome (CRS)-renal injury during heart failure (HF)-is linked to higher morbidity. Whether circulating extracellular vesicles (EVs) and their RNA cargo directly impact its pathogenesis remains unclear. METHODS: We investigated the role of circulating EVs from patients with CRS on renal epithelial/endothelial cells using a microfluidic kidney-on-chip model (KOC). The small RNA cargo of circulating EVs was regressed against serum creatinine to prioritize subsets of functionally relevant EV miRNAs and their mRNA targets investigated using in silico pathway analysis, human genetics, and interrogation of expression in the KOC model and in renal tissue...
September 14, 2023: JCI Insight