Increase of circulating miR-223 and insulin-like growth factor-1 is associated with the pathogenesis of acute ischemic stroke in patients
- Equal contributors
1 Department of neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Ruijin Er Road, 200025 Shanghai, China
2 Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Hua Shan Road, 200030 Shanghai, China
BMC Neurology 2014, 14:77 doi:10.1186/1471-2377-14-77Published: 8 April 2014
The relationship between circulating microRNA-223 and pathogenesis of acute ischemic stroke is unknown. Here we investigated the roles and possible targets of circulating microRNA-223 in human ischemic stroke within the first 72 hours.
Blood samples were collected from patients within 72 hours after cerebral ischemia (n = 79) and compared with healthy control samples (n = 75). The level of possible downstream factors of microRNA-223 including insulin-like growth factor-1, insulin-like growth factor-1 receptor and interleukin-6 was examined by ELISA assay. The relationship between the microRNA-223 level and NIHSS scores, TOAST subtypes, and infarct volume was analyzed respectively. In addition, twelve adult male CD-1 mice underwent middle cerebral artery occlusion using the suture technique. Circulating blood and brain tissue in the ischemic ipsilateral hemisphere were collected at 24 hours after middle cerebral artery occlusion. microRNA-223 was detected by real-time polymerase chain reactions.
microRNA-223 levels in the circulating blood of acute ischemic stroke patients were greatly increased compared to the control (p < 0.05). microRNA-223, which were negatively correlated with NIHSS scores (r = −0.531, p < 0.01) and infarct volume (r = −0.265, p = 0.039), was significantly up-regulated in large artery and small artery strokes. The plasma level of insulin-like growth factor-1 was positively associated with that of microRNA-223 (r = 0.205, p = 0.022). Moreover, microRNA-223 in blood and brain were positively correlated (r = 0.834, p < 0.05), and they were up-regulated significantly in mice that underwent middle cerebral artery occlusion (p < 0.05).
Our results suggest that microRNA-223 is associated with acute ischemic stroke and possibly plays a role in stroke through up-regulating growth factor such as insulin-like growth factor-1 gene.