Chronic cerebral hypoperfusion (CCH) is a high-risk factor of Alzheimer's disease (AD). MicroRNAs (miRNAs) are ideal mediators of hypoxic stress responses to facilitate cellular adaptation to long-term hypoxia. MiR-124 is a kind of nervous system-specific miRNAs, and one of its target genes is β-site amyloid precursor protein cleaving enzyme 1 (BACE1). In the present study, miR-124 was found to be inhibited all the time from early to late stage of cerebral hypoxia accompanying with the upregulation of BACE1 protein and overproduction of amyloid-β (Aβ) in the hippocampus from cerebral hypoperfusion rat models. Meanwhile, Aβ could further enhance the expression of BACE1 protein due to the inhibition of miR-124. Thus, miR-124 was the key factor in this hypoxia/Aβ-miR-124-BACE1-Aβ cycle. The activation of EPAC-Rap1 pathway was involved in the inhibition of miR-124 in hippocampus under hypoxia or Aβ insult. Our data suggest that, as an endogenous regulator of BACE1 protein, miR-124 may play a role in AD onset induced by CCH.
Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp atent foramen ovale (PFO) is an anatomical variant of the interatrial septum with an overall prevalence of 27% in autopsy studies. 1 PFO has been associated with cryptogenic stroke and migraine headaches, 2-4 and increasingly recognized as a source of paradoxical embolism. A high prevalence of PFO has been reported in approximately 50% of patients with cryptogenic transient ischemic attack (TIA) or ischemic stroke, 2 suggesting an association between the presence of PFO, with or without atrial septal aneurysm (ASA), and thromboembolic events (TE). 5 The optimal management for the prevention of a paradoxical embolic event in these patients remains controversial. Medical therapies with anticoagulants or antiplatelet agents, surgical PFO closure and percutaneous transcatheter closure of the PFO have been proposed as therapeutic options. 6 The results of several randomized clinical trials, randomized controlled trials and reports of single-center experience have indicated that transcatheter PFO closure is a potential option for patients with PFO and thromboembolic phenomena, in that it avoids the morbidity associated with surgical closure or lifelong anticoagulation therapy. 4,7-10 Despite the good short-term results of transcatheter PFO closure in these patients, however, the long-term data are limited, especially in Chinese patients. The aim of the present study was therefore to assess the long-term clinical outcome in PFO patients with paradoxical embolism who underwent transcatheter PFO closure in a single center.
Methods
PatientsBetween January 2005 and May 2010, 192 patients who were referred for transcatheter closure of a PFO following 1 or more presumed paradoxical systemic events were included in the present study. A TE was considered to be due to a paradoxical embolism when the following criteria were met: presence of PFO with spontaneous or provocable right-to-left shunt during transthoracic echocardiography (TTE)/trans-
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