Reference : MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/148443
MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy.
English
Halkein, Julie [Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
Tabruyn, Sebastien P. [> >]
Ricke-Hoch, Melanie [> >]
Haghikia, Arash [> >]
Nguyen, Ngoc-Quynh-Nhu [> >]
Scherr, Michaela [> >]
Castermans, Karolien [> >]
Malvaux, Ludovic [> >]
Lambert, Vincent mailto [Centre Hospitalier Universitaire de Liège - CHU > > Ophtalmologie >]
Thiry, Marc mailto [Université de Liège - ULiège > Département des sciences de la vie > Biologie cellulaire >]
Sliwa, Karen [> >]
Noël, Agnès mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Martial, Joseph mailto [Université de Liège - ULiège > Département des sciences de la vie > Département des sciences de la vie >]
Hilfiker-Kleiner, Denise [> >]
Struman, Ingrid mailto [Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire >]
2013
Journal of Clinical Investigation
123
5
2143-54
Yes (verified by ORBi)
International
0021-9738
United States
[en] Peripartum cardiomyopathy (PPCM) is a life-threatening pregnancy-associated cardiomyopathy in previously healthy women. Although PPCM is driven in part by the 16-kDa N-terminal prolactin fragment (16K PRL), the underlying molecular mechanisms are poorly understood. We found that 16K PRL induced microRNA-146a (miR-146a) expression in ECs, which attenuated angiogenesis through downregulation of NRAS. 16K PRL stimulated the release of miR-146a-loaded exosomes from ECs. The exosomes were absorbed by cardiomyocytes, increasing miR-146a levels, which resulted in a subsequent decrease in metabolic activity and decreased expression of Erbb4, Notch1, and Irak1. Mice with cardiomyocyte-restricted Stat3 knockout (CKO mice) exhibited a PPCM-like phenotype and displayed increased cardiac miR-146a expression with coincident downregulation of Erbb4, Nras, Notch1, and Irak1. Blocking miR-146a with locked nucleic acids or antago-miRs attenuated PPCM in CKO mice without interrupting full-length prolactin signaling, as indicated by normal nursing activities. Finally, miR-146a was elevated in the plasma and hearts of PPCM patients, but not in patients with dilated cardiomyopathy. These results demonstrate that miR-146a is a downstream-mediator of 16K PRL that could potentially serve as a biomarker and therapeutic target for PPCM.
http://hdl.handle.net/2268/148443
10.1172/JCI64365
http://reflexions.ulg.ac.be/PPCM

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
halkein_tabruyn_hoch_JCI2013.pdfPublisher postprint4.44 MBView/Open

Additional material(s):

File Commentary Size Access
Open access
halkein rev2 suppl figure+legendes final.pdfsuppl figures961.43 kBView/Open
Open access
Halkein JCI rev2_Supplementary data.pdfsuppl data222.54 kBView/Open

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.