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2016 ; 21
(ä): 16
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Posttranscriptional and transcriptional regulation of endothelial nitric-oxide
synthase during hypoxia: the role of microRNAs
#MMPMID28536619
Kalinowski L
; Janaszak-Jasiecka A
; Siekierzycka A
; Bartoszewska S
; Wo?niak M
; Lejnowski D
; Collawn JF
; Bartoszewski R
Cell Mol Biol Lett
2016[]; 21
(ä): 16
PMID28536619
show ga
Understanding the cellular pathways that regulate endothelial nitric oxide (eNOS,
NOS3) expression and consequently nitric oxide (NO) bioavailability during
hypoxia is a necessary aspect in the development of novel treatments for
cardiovascular disorders. eNOS expression and eNOS-dependent NO cellular
signaling during hypoxia promote an equilibrium of transcriptional and
posttranscriptional molecular mechanisms that belong to both proapoptotic and
survival pathways. Furthermore, NO bioavailability results not only from eNOS
levels, but also relies on the presence of eNOS substrate and cofactors, the
phosphorylation status of eNOS, and the presence of reactive oxygen species (ROS)
that can inactivate eNOS. Since both NOS3 levels and these signaling pathways can
also be a subject of posttranscriptional modulation by microRNAs (miRNAs), this
class of short noncoding RNAs contribute another level of regulation for NO
bioavailability. As miRNA antagomirs or specific target protectors could be used
in therapeutic approaches to regulate NO levels, either by changing NOS3 mRNA
stability or through factors governing eNOS activity, it is critical to
understand their role in governing eNOS activity during hypoxa. In contrast to a
large number of miRNAs reported to the change eNOS expression during hypoxia,
only a few miRNAs modulate eNOS activity. Furthermore, impaired miRNA biogenesis
leads to NOS3 mRNA stabilization under hypoxia. Here we discuss the recent
studies that define miRNAs' role in maintaining endothelial NO bioavailability
emphasizing those miRNAs that directly modulate NOS3 expression or eNOS activity.