A growing number of studies have suggested microRNAs (miRNAs) are involved in the modulation of myocardial ischemia-reperfusion (MI/R) injury; however, the role of endogenous miRNAs targeting endothelial cells (ECs) and its interaction with ICAM-1 in the setting of MI/R remain poorly understood. Our microarray results showed that miR-146a, miR-146b-5p, miR-155*, miR-155, miR-497, and miR-451 were significantly upregulated, whereas, miR-141 and miR-564 were significantly downregulated in the ECs challenged with TNF-α for 6 h. Real-time PCR analyses additionally validated that the expression levels of miR-146a, miR-155*, and miR-141 were consistent with the microarray results. Then, ICAM-1 was identified as a novel target of miR-141 by Target Scan software and the reporter gene system. Further functional experiments showed that elevated levels of miR-141 inhibited ICAM-1 expression and diminished leukocytes adhesion to ECs in vitro. In an in vivo murine model of MI/R injury, pretreatment with miR-141 mimics through the tail vein downregulated the expression level of ICAM-1 in heart and attenuated MI/R injury as evidenced by decreased infarct size and decline of serum cardial troponin I (cTnI) and lactate dehydrogenase (LDH) concentration. The cardioprotective effects of miR-141 mimics may be attributed to the decreased infiltration of CD11b(+) cells and F4/80(+) macrophages into ischemic myocardium tissue. In conclusion, our results demonstrate that miR-141, as a novel repressor of ICAM-1, is involved in the attenuation of MI/R injury via antithetical regulation of ICAM-1 and inflammatory cells infiltration. Thus miR-141 may constitute a new therapeutic target in the setting of ischemic heart disease.

Stimuli-responsive nanoporous membranes have attracted increasing interest in various fields due to their abrupt changes of permeation/separation in response to the external environment. Here we report ultrathin pH-sensitive nanoporous membranes that are easily fabricated by the self-assembly of poly(acrylic acid) (PAA) in a metal hydroxide nanostrand solution. PAA-adsorbed nanostrands (2.5-5.0 nm) and PAA-Cu(II) nanogels (2.0-2.5 nm) grow competitively during self-assembly. The PAA-adsorbed nanostrands are deposited on a porous support to fabricate ultrathin PAA membranes. The membranes display ultrafast water permeation and good rejection as well as significant pH-sensitivity. The 28 nm-thick membrane has a water flux decrease from 3740 to 1350 L m(-1)  h(-1)  bar(-1) (pH 2.0 to 7.0) with a sharp decrease at pH 5.0. This newly developed pH-sensitive nanoporous membranes may find a wide range of applications such as controlled release and size- and charge-selective separation.