Endothelial progenitor cell miR-126 promotes homing of endothelial progenitor cells within arterial thrombus in patients with cerebral infarction and its molecular mechanism.

OBJECTIVE: The present study was designed to investigate the effect of microRNA-126 (miR-126) on the migration and homing of endothelial progenitor cells (EPCs) within arterial thrombus of cerebral infarction patients. MATERIALS AND METHODS: EPCs from rat bone marrow were isolated, and miR-126 overexpressed EPCs were constructed by lentiviral transfection. Then, the middle cerebral artery occlusion (MCAO) model was established by the method of thread ligation. Successfully established model rats were randomly divided into miR-126 overexpression EPC group, miR-126 wild type EPC group, and normal saline group. One day after the infarction, the miR-126 overexpression EPCs, miR-126 wild type EPCs, and normal saline, were injected into the lateral ventricle of the corresponding groups. Also, the transplanted cells were tracked by cell dye SPDiIC18. The expression of tight junction proteins ZO-1 and Claudin-5 in brain tissue was detected by Western blotting. RESULTS: Transplanted cells were detected in the cerebral infarction area 3 days after transplantation by cell dye SP-DiIC18. The number of homing EPCs in miR-126 overexpression group was significantly higher than that of miR-126 wild type EPC group (p < 0.05). Also, the protein expression of ZO-1 and Claudin-5 in the miR- 126 overexpression EPC group was significantly higher compared with that of the miR-126 wild type EPC group and the normal saline group. CONCLUSIONS: miR-126 overexpression EPCs, which were transplanted in the lateral ventricle, can home to the cerebral infarction areas via increasing increase.

The curative effect comparison of two kinds of therapeutic regimens on decreasing the relative intensity of microembolic signal in CLAIR trial.

BACKGROUND: Microembolic signals (MESs) are direct markers of unstable large artery atherosclerotic plaques. In a previous study, we found that the number of MESs is associated with stroke recurrence and that clopidogrel plus aspirin more effectively reduce the number of MESs than does aspirin alone. Stroke recurrence is associated with not only the number of MESs but also the size of the MES, which can theoretically be estimated by monitoring the MES intensity via transcranial doppler (TCD). Thus, we compared the effects of clopidogrel and aspirin with aspirin alone on MES intensity using TCD. METHODS: We recruited 100 patients who experienced acute ischemic stroke or transient ischemic attack (TIA) within 7days of symptom onset. All patients also had large artery stenosis in the cerebral or carotid arteries and the presence of MES as revealed by TCD. The patients were randomized to receive either aspirin or clopidogrel and aspirin for 7days. MES monitoring was performed on days 2 and 7. RESULTS: Intent-to-treat (ITT) analysis (46 patients in the dual therapy group, 52 patients in the monotherapy group) and per-protocol (PP) analysis (25 patients in the dual therapy group, 31 patients in the monotherapy group) were performed on 98 patients. The primary finding was that the MES intensity was dramatically reduced in the dual therapy group. ITT analysis of the dual therapy group revealed that the MES intensity was 8.04 (0-16) dB before treatment, 0.00 (0-17) dB on day 2, and 0.00 (0-12) dB on day 7 (P=0.000). In the monotherapy group, the MES intensity was 9.00 (0-20) dB before treatment, 8.25 (0-17) dB on day 2, and 7.0 (0-18) dB on day 7 (P=0.577). PP analysis revealed similar results. No severe hemorrhagic complications were detected. The two patients in this study who experienced stroke recurrence were in the monotherapy group. CONCLUSIONS: Clopidogrel and aspirin more effectively decrease the MES intensity than aspirin alone in patients with large artery stenotic minor stroke or TIA.