Circulating microRNAs and vascular calcification in hemodialysis patients

Vascular calcification is commonly observed in patients with chronic kidney disease (CKD), and accumulating evidence indicates that its prevalence and severity correlate with long-term outcomes such as mortality in CKD.1,2 Therefore, the means of preventing the development and progression of vascular calcification has become an important issue of CKD care. There are multiple pathogenic mechanisms associated with vascular calcification.3 Among patients with CKD, several uremia-related factors contribute to its development. Hyperphosphatemia is a well-recognized abnormality of the CKD bone and mineral disorder, and clinical studies have indicated that phosphate blood levels are an important prognostic factor of both all-cause and cardiovascular mortality.4,5 Additionally, uremic hyperparathyroidism, chronic inflammation, and the accumulation of uremic toxins are all caused by renal dysfunction and usually observed in the early stages of CKD.6 MicroRNAs (miRs) are a family of small, non-coding RNAs that play key roles in modulating gene expression by degrading or repressing mRNAs through effects on cell proliferation, differentiation, and apoptosis.7 Recent animal studies observed that several miRs, such as miR223 and miR21, are involved in vascular smooth muscle cell inflammation and arterial calcification.7–9 Higher levels of miR223 were observed in CKD with atherosclerotic vessels,8 and higher miR21 levels were detected in atherosclerotic arteries.7 Furthermore, clinical studies showed that both lower and higher blood levels of certain miRs were associated with uremic vascular calcification10 and atherosclerosis.11 However, the functional role of these miRs has not been thoroughly investigated. In the present study, we aimed to measure the levels of several selected circulating miRs and to determine the relationship between their levels and the presence of vascular calcification. The role of circulating miRs in the severity of vascular calcification was also explored.