MicroRNA 499 gene expression in patients on hemodialysis with cardiovascular complications.

Abstract

MicroRNA (miRNA) 499 is an evolutionarily conserved muscle-specific miRNA that is encoded by an intron of the myh7 gene and is likely to play a role in myosin gene regulation. It has been shown to be involved in inhibiting apoptosis and myocardial infarction induced by ischemia and anoxia. It is unknown whether levels of miRNAs are affected in patients undergoing hemodialysis. The aim of this study was to assess circulating levels of miRNA 499 in hemodialysis patients and whether the levels are affected by dialyzer membranes (high flux vs. low flux). The studied population consisted of 32 end stage renal disease (ESRD) patients (22 males and 10 females) with age ranged from 38% to 75% years on regular hemodialysis (4 hours, 3 times weekly) for at least 1 year duration with cardiovascular events in the last 6 months and 32 healthy controls (20 males and 12 females) with an age range from 54 to 60 years. Patients were involved into a two-stage sequential study; high-flux hemodialysis stage (stage I), then low-flux hemodialysis stage (stage II). Expressed levels of plasma miRNA 499 have been measured by Real Time-PCR. Lipid profile, serum phosphorus, serum calcium, serum creatinine, and blood urea were measured in all patients. In this study, 2 patients with an open-heart surgery showed highly elevation in the miRNA 499, while the other patients, showing different degrees of ischemia, had different levels of elevated miRNA 499. Statistically significant higher levels of miRNA 499 in plasma were observed in all the studied patients with cardiovascular diseases compared to the levels of miRNA 499 found in healthy controls (P < 0.0001). MicroRNA 499 was found to be a dialyzable marker. A significant decrease in plasma levels of miRNA 499 was obtained after either high-flux or low-flux dialysis compared to plasma levels of miRNA 499 found before dialysis (P < 0.0001). On comparing both types of hemodialysis membranes with respect to miRNA 499 clearance, we found that low-flux membrane showed better clearance for miRNA 499 than high-flux membrane with a statistically significant difference between them (P < 0.001). In conclusion, miRNA 499 levels are elevated in patients with ESRD with cardiovascular complications. High-flux membrane seems to be less efficient in miRNA 499 clearance in cardiac patients on hemodialysis.