MicroRNAs Are Associated with Uremic Toxicity, Cardiovascular Calcification, and Disease

Background: Vascular calcification has been recognized to be a major risk factor in chronic kidney disease (CKD) and downstream cardiovascular complications. Micro-RNAs (miRNAs) are small noncoding RNAs comprising 20-25 nucleotides that regulate gene expression by inhibiting or degrading the target mRNA, and constitute potential new biomarkers and future therapeutic strategies. Summary: We tested the relevance of several cardiovascular-specific miRNAs as new biomarkers for CKD, cardiovascular disease, and cardiovascular complications. We have shown, in murine models, that miR-126, miR-143, miR-145, and miR-223 levels and the levels of their specific targets are modulated during the crucial stages of CKD and atherosclerosis. In addition, miRNA levels were correlated with classical biomarkers of CKD and atherosclerosis such as cholesterol, urea, and calcium levels. Dysregulation of these same miRNAs was observed in the serum of CKD, hemodialyzed, and kidney transplant recipients. We also demonstrated correlations between serum miRNAs and uremic toxins. We therefore suggest that miR-126, miR-143, miR-145, and miR-223 are potential biomarkers of vascular calcification and cardiovascular disease associated with CKD. Key Messages: The identification of new biomarkers that can improve the diagnosis and monitoring of CKD and cardiovascular disease patients is crucial in modern medicine. Our data could be particularly useful in the management of cardiovascular disease associated with CKD, provide new light in the understanding of the molecular events underlying cardiovascular disease and cardiovascular calcification, and possibly be used as a treatment strategy to prevent these diseases.