Журнал канцерогенеза и мутагенеза

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A Novel Biomarker MicroRNA-92a-3p as a Link between Cardiovascular Disease and Chronic Kidney Disease

Kazumi Fujioka

The emergence of microRNAs (miRNA) as significant regulators of pathophysiological processes has provided new therapeutic strategies in atherosclerotic status. Recently, the author has described that microRNA-92a-3p (miR-92a-3p), having pleiotropic manner is a potential therapeutic target in atherosclerosis-related diseases. The author has previously described that mild renal dysfunction was associated with endothelial dysfunction in women and that the cardio-renal interrelationship may be also suggested under mild renal dysfunction. Shang et al. suggested mcroiRNA-92a (miR-92a) as a crucial link between chronic kidney disease (CKD) and cardiovascular disease (CVD) by mediating uremia-impaired endothelial dysfunction. On the evidences of relationships between miR-92a and flowmediated vasodilation (FMD) and between miR-92a and estimated glomerular filtration rate (eGFR) level, the author indicates that miR-92a gene expression profile in endothelial cell and the circulating level reflecting FMD study and eGFR level which were established indicators may be an early diagnostic biomarker in atherosclerosis-related CKD, having a link between CVD and CKD. Shang et al. also indicated miR-92a as a link among CKD-induced uremia, oxidative stress, and endothelial dysfunction. On the proof of the interrelationship among miR-92a profile, FMD study, and eGFR level, the author suggests that atherosclerosis-related CKD cause oxidative stress, leading to miR-92a expression, endothelial dysfunction, and renal dysfunction. In CKD with advanced stage, oxidative stress derived from uremic toxin mainly contributes to miR-92a gene expression profile, endothelial dysfunction, and renal failure. Wiese et al. showed that renal injury significantly increased endothelial miR-92a-3p and dual inhibition of miR-92a-3p and miR-489-3p significantly reduced atherosclerotic lesion compared to control, thereby, suggesting that miR-92a-3p and/or miR-489-3p are potential therapeutic targets in atherosclerosis-related CKD. The author emphasizes that clinically and genetically, the studies have provided a link between CVD and CKD mediated by endothelial dysfunction even at early stage.