Altered Plasma MicroRNAs as Novel Biomarkers for Arteriosclerosis Obliterans

Aim: Arteriosclerosis obliterans (ASO) of the lower extremities is a major cause of adult limb loss worldwide. A timely diagnosis in the early stages of the disease determines the clinical outcomes, however lacking of palpable symptoms remains the biggest obstacle. This study aimed to screen a cluster of MicroRNAs (miRNAs) that can be used as biomarker for the ASO in the earlier stages.

Methods: Plasma from 3 patients with ASO and 3 healthy controls were profiled to screen altered miRNAs by microarray, then Real time PCR was further used to confirm the changes in 55 ASO patients and 54 controls.We also analyzed the correlation of miRNAs level with Fontaine stages and the influence of T2DM which is a common complication with ASO on the level of miRNAs.

Result: Twenty-four aberrantly expressed miRNAs were screened in the plasma of ASO patients. Real time PCR verified that the level of miR-4284 was significantly increased, while levels of miR-4463, miR-4306 and miR-221-3p were significantly decreased both in the plasma and in the sclerotic samples compared with the controls. Interestingly, we revealed a time and stage specific expression manner, as shown that expression of miR-4284 increased at the stage I of ASO and maintained the tendency to stage IV, while miR-4463 expression decreased at every stage of ASO; however, the expression of miR-4463 showed opposite changes in ASO patients with or without T2DM.

Conclusion: Altered expressions of miR-4284 and miR-4463 are novel characteristics and may serve as potential biomarkers for the early diagnosis of ASO.